Catechin promotes the germination of Pistacia chinensis seeds via GA biosynthesis.

BACKGROUND AND AIMS: Chinese pistachio (Pistacia chinensis), an important horticultural plant species, holds great ornamental value with beautiful leaves and fruits. Seedling propagation of this tree species is restricted by its erratic seed germination; however, the germination mechanism is ambiguous. The aim of this study was to determine the germination mechanism from a novel perspective based on the multi-omics data. METHODS: The multi-omics technique combined with hormone content measurement was applied to seed germination of Chinese pistachio. KEY RESULTS: Due to its great accumulation during seed germination, catechin stood out from the identified metabolites in a broadly targeted metabolomic analysis. Exogenous catechin at 10 mg L-1 significantly improved the germination of Chinese pistachio seeds. An interesting result of hormone analysis was that the improving effect of catechin could be attributed to an increase in gibberellic acid 3 (GA3) content rather than a decrease in abscisic acid (ABA) content before germination. Treatments with paclobutrazol (PAC, a GA biosynthesis inhibitor) and PAC + catechin also showed that the promoting effect of catechin on seed germination depends on GA biosynthesis. Transcriptome analysis and qRT‒PCR further revealed that catechin induced the expression of PcGA20ox5 to activate GA biosynthesis. Several transcription factors were induced by catechin and GA treatments, such as TCP, bZIP and C3H, which may play an important regulatory role in GA biosynthesis in a catechin-mediated way. CONCLUSIONS: Catechin promotes seed germination via GA biosynthesis in Chinese pistachios. This study proposes a novel mechanism by which catechin promotes seed germination via the GA pathway, which provides new insight into a comprehensive understanding of seed dormancy and germination.

Contrast sensitivity and comfort levels with different types of polarised glasses under steady glare.

The influence of various polarised glasses on visual performance is crucial due to their widespread. This study measured the visual contrast sensitivity (CS) of dominant eyes by quick contrast sensitivity function (qCSF) procedure at 10 spatial frequencies and 3 noise levels under nonglare, steady glare, steady glare with night lenses, and steady glare with day&night lenses, respectively. Later, the second experiment measured the subjects' subjective feelings under these four viewing conditions. The results showed that there was no significant difference in the CS between the two conditions with polarised glasses and the steady glare. However, the subjects reported greater comfort with glasses than without them. These results suggest that there was an underlying bias when people rated the polarised glasses, and the qCSF procedure was a useful tool for evaluating visual performance.

Whether polarised glasses can relieve the impairment of steady glare on contrast sensitivity over multi-spatial frequency and external noise levels is unaddressed. Using the quick CSF method, we revealed that CS declines with steady glare but polarised lenses don't significantly relieve it. However, subjects reported increased comfort, suggesting a perceptual bias.

Biomimetic liposomal nanozymes improve breast cancer chemotherapy with enhanced penetration and alleviated hypoxia.

BACKGROUND: Doxorubicin (Dox) has been recommended in clinical guidelines for the standard-of-care treatment of breast cancer. However, Dox therapy faces challenges such as hypoxia, acidosis, H2O2-rich conditions and condensed extracellular matrix in TME as well as low targeted ability. METHODS: We developed a nanosystem H-MnO2-Dox-Col NPs based on mesoporous manganese dioxide (H-MnO2) in which Dox was loaded in the core and collagenase (Col) was wrapped in the surface. Further the H-MnO2-Dox-Col NPs were covered by a fusion membrane (MP) of inflammation-targeted RAW264.7 cell membrane and pH-sensitive liposomes to form biomimetic MP@H-MnO2-Dox-Col for in vitro and in vivo study. RESULTS: Our results shows that MP@H-MnO2-Dox-Col can increase the Dox effect with low cardiotoxicity based on multi-functions of effective penetration in tumor tissue, alleviating hypoxia in TME, pH sensitive drug release as well as targeted delivery of Dox. CONCLUSIONS: This multifunctional biomimetic nanodelivery system exhibited antitumor efficacy in vivo and in vitro, thus having potential for the treatment of breast cancer.

Research and Application of Kupffer Cell Thresholds for BSA Nanoparticles.

Over the past decade, the dose of nanoparticles given to solid tumors has remained at a median of 0.7% of the injected dose. Most nanoparticles are trapped in a mononuclear phagocyte system (MPS), of which 85% are Kupffer cells. In our study, threshold doses of bovine serum albumin (BSA) nanoparticles were investigated for the uptake of Kupffer cells in vitro and in vivo. The antitumor effect and safety of albumin-bound paclitaxel (ABP) were improved by using threshold doses of BSA nanoparticles. We found a threshold dose of 20,000 nanoparticles per macrophage uptake in vitro and a saturation dose of 0.3 trillion nanoparticles in tumor-bearing mice. In vivo efficacy and safety evaluations demonstrated that the threshold doses of blank BSA nanoparticles could significantly improve the efficacy and safety of ABP against tumors compared with ABP alone. In this study, the delivery efficiency of ABP was improved by using blank nanoparticles to saturate Kupffer cells, which provided a new approach to studying the Kupffer cell saturation threshold and thus a new scheme for improving the curative effect of ABP.

Classification of diterpenoid alkaloids from Aconitum kusnezoffii Reichb. by liquid chromatography-tandem mass spectrometry-based on molecular networking.

Trace amounts of components in traditional Chinese medicine are considered pharmacological active substances used for treating many serious diseases. However, purifying all the trace substances and making clear their structures are not easy. In this context, high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry based molecular networking was applied to investigate the chemical constituents of the roots of Aconitum kusnezoffii Reichb., which led to the identification of 33 nodes in different groups (N1-N33). Based on the excremental fragmentation pathway of known diterpenoid alkaloids (1-9) and comparisons of characteristic ions and characteristic loss of analogs in literature, the structures of unknown ions were deduced. This work lays a foundation for the evaluation of the clinical basis and mechanism of traditional Chinese medicine from the aspects of chemistry. In this paper, the method speculation of unknown natural products by means of molecular network method is expected to be applied in the discovery and change law of relevant active components in clinical pharmacology and the change of complex systems caused by trace active compounds.

[Research progress on chemical constituents and pharmacological studies on root bark of Lycium barbarum].

Lycii Cortex, the dry root bark of Lycium barbarum(Solanaceae), is rich in chemical compositions with unique structures, such as organic acids, lipids, alkaloids, cyclopeptides and other components, and plays an important role in traditional Chinese medicine. It has the effect of cooling blood and removing steam, clearing lung and reducing fire. It is mainly used in the treatment of hot flashes due to Yin deficiency, hectic fever with night sweat, cough, hemoptysis and internal heat and diabetes. Modern pharmacological studies have shown that the crude extract or monomer of Lycii Cortex has a variety of pharmacological activities, such as hypoglycemic, hypotensive, hypolipidemic, antibacterial, and antiviral effects. In this paper, the chemical constituents and pharmacological effects of Cortex Lycii were reviewed in order to further clarify its effective substances, promote the development of medical undertakings, and ensure the "Healthy China" plan.

[A new 9,19-cycloartane glycoside from Asplenium ruprechtii].

Chemical constituents of water extracts of Asplenium ruprechtii were investigated. Five compounds were isolated by silica gel, Sephadex LH-20 gel column chromatographies and preparative HPLC, and their structures were identified by various spectral analyses as aspleniumside G(1), trans-p-coumaric acid(2), trans-p-coumaric acid 4-O-ß-D-glucoside(3), cis-p-coumaric acid 4-O-ß-D-glucoside(4), and(E)-ferulic acid-4-O-ß-D-glucoside(5). Among them, compound 1 is a new 9,19-cycloartane glycoside.

Structural Determination of a New Cycloartane Glycoside from Asplenium ruprechtii.

We characterized a new cycloartane glycoside, herein known as aspleniumside F (1), along with five known compounds as kaempferol-3-O-[(6-O-(E)-feruloyl)-ß-D-glucopyranosyl]-(1→2)-ß-D-galacopyranoside (2), quercetin-3-O-[(6-O-(E)-feruloyl)-ß-D-glucopyranosyl]-(1→2)-ß-D-glucopyranoside (3), kaempferol-3-O-[(6-O-(E)-caffeoyl)-ß-D-glucopyranosyl]-(1→2)-ß-D-glucopyranoside (4), kaempferol-3-O-[(6-O-(E)-caffeoyl)-ß-D-glucopyranosyl]-(1→2)-ß-D-glucopyranosyl-7-O-ß-D-glucopyranoside (5), and kaempferol-3-O-[(6-O-p-coumaroyl)-ß-D-glucopyranosyl]-(1→2)-ß-D-glucopyranosyl-7-O-ß-D-glucopyranoside (6), from Asplenium ruprechtii Sa. Kurata, a folk medicine widely used to treat Thromboangiitis obliterans in China, Japan, and Korea. Based on spectroscopic, mainly 1D-, 2D-NMR and (+)-HR-ESI-MS, analyses as well as through comparisons with previous reports, its chemical structure was determined as 3ß,24,30-tri-ß-D-glucopyranosyl-23,25-dihydroxycycloartane (= (23R,24R)-3ß,24-bis-(ß-D-glucopyranosyloxy)-23,25-dihydroxy-9ß-9,19-cyclolanostan-29-yl ß-D-glucopyranoside). According to the 1 H coupling constant of anomeric protons and co-TLC of the acid hydrolysate with D-glucose, all three glycoside groups in 1 were revealed as ß-D-glucopyranosyl. Furthermore, SOD-like antioxidant activity evaluation via IC50 of 12.43, 6.78, 9.12, 6.94 and 4.85 µM revealed that compounds 2-6 had bioactivity.

Novel role for non-homologous end joining in the formation of double minutes in methotrexate-resistant colon cancer cells.

BACKGROUND: Gene amplification is a frequent manifestation of genomic instability that plays a role in tumour progression and development of drug resistance. It is manifested cytogenetically as extrachromosomal double minutes (DMs) or intrachromosomal homogeneously staining regions (HSRs). To better understand the molecular mechanism by which HSRs and DMs are formed and how they relate to the development of methotrexate (MTX) resistance, we used two model systems of MTX-resistant HT-29 colon cancer cell lines harbouring amplified DHFR primarily in (i) HSRs and (ii) DMs. RESULTS: In DM-containing cells, we found increased expression of non-homologous end joining (NHEJ) proteins. Depletion or inhibition of DNA-PKcs, a key NHEJ protein, caused decreased DHFR amplification, disappearance of DMs, increased formation of micronuclei or nuclear buds, which correlated with the elimination of DHFR, and increased sensitivity to MTX. These findings indicate for the first time that NHEJ plays a specific role in DM formation, and that increased MTX sensitivity of DM-containing cells depleted of DNA-PKcs results from DHFR elimination. Conversely, in HSR-containing cells, we found no significant change in the expression of NHEJ proteins. Depletion of DNA-PKcs had no effect on DHFR amplification and resulted in only a modest increase in sensitivity to MTX. Interestingly, both DM-containing and HSR-containing cells exhibited decreased proliferation upon DNA-PKcs depletion. CONCLUSIONS: We demonstrate a novel specific role for NHEJ in the formation of DMs, but not HSRs, in MTX-resistant cells, and that NHEJ may be targeted for the treatment of MTX-resistant colon cancer.

[Study on congenital cardiac anomalies induced by arsenic exposure before and during maternal pregnancy in fetal rats].

OBJECTIVE: To investigate the effects of arsenic exposure before and during maternal pregnancy on heart development of fetal rats. METHODS: According to body weight, thirty-two female SD rats (30 to 40 days of age) were randomly divided into control group, low dose group, middle dose group and high dose group with 8 rats per group. They were allowed free access to drinking water with 0, 37.5, 75 and 150 mg/L of sodium arsenite (NaAsO2) for 6 weeks, respectively. Then all the female rats and adult male SD rats were caged together for mating. Once female rats were determined to be pregnant, they would continue to drink deionized distilled water containing different concentrations of sodium arsenite for another 2 weeks. On embryonic day 16, rats were sacrificed to harvest fetuses. Female rats' weight changes, abortions, absorbed fetus number, growth and development of fetal rats were observed. Hematoxylin-eosin staining of serial cardiac slices was performed in embryos to observe cardiac morphology and structure. Fur arsenic contents of female rats were determined with the method of atomic fluorescence spectrometry. RESULTS: Subchronic arsenic exposure caused slow weight growth in female rats. There were two cases of abortion in middle dose group and high dose group, respectively. Compared with these of control group, fetal and placental weight decreased (P < 0.05), and the incidence of fetal absorption increased (P < 0.05) in all arsenic-treated groups. Cardiac malformations in fetal rats including ventricular septal defect, atrial septal defect and tetralogy of Fallot were observed in low, middle and high dose group. The incidence of cardiac malformations increased with the increase of arsenic concentrations in drinking water. Compared with that of control group, the incidence of cardiac malformations remarkably increased in both middle and high dose groups (P < 0.05). Fur arsenic contents increased with the increase of arsenic concentrations in drinking water (P < 0.01). CONCLUSION: Arsenic exposure before and during maternal pregnancy could cause abnormal cardiac development in fetal rats, and increased the risk of congenital heart disease.

[Analysis of relevant factors for recurrence of ovarian endometriosis after conservative laparoscopic surgery].

OBJECTIVE: To analyze relevant factors for recurrence of ovarian endometriosis after conservative surgery.
 METHODS: A cohort study was performed on 310 patients who had performed conservative surgery for ovarian endometriosis. All patients underwent clinical interview. The relevant factors included: age at surgery, clinical symptom and signs, medical history, gynecologic examination, preoperative gravidity, complication, adenomyosis, American Society for Reproductive Medicine (ASRM) scores, post-operative drug therapy, post-operative gravidity and so on. The logistic regression analysis was performed to determine the predictive factors for recurrence of endometriosis.
 RESULTS: The relevant factors by univariate analysis were determined. The history of endometriosis surgery, history of intrauterine operation, tenderness nodule at cal-de-sal, bilateral endometrioma, multilocular cyst, intraoperative ASRM scores, complication of adenomyosis and operation time were the risk factors; whereas pre- and post-operative gravidity, post-operative drug therapy, and age at surgery were the protective factors. Meanwhile, the relevant factors by multivariate analysis were also confirmed. The history of endometriosis surgery, history of intrauterine operation, tenderness nodule at cal-de-sal, bilateral endometrioma, multilocular cyst, and intraoperative ASRM scores were the risk factors; whereas post-operative gravidity, post-operative drug therapy, pre-operative gravidity, and age at surgery were the protective factors.
 CONCLUSION: The risk factors for recurrence of ovarian endometriosis are history of endometriosis surgery, history of intrauterine operation, tenderness nodule at cal-de-sal, bilateral endometrioma, multilocular cyst, intraoperative ASRM scores, whereas the protective factors are pre- and post-operative gravidity, post-operative drug therapy and age at surgery.

[Targeted interruption of COX-2 gene by siRNA inhibits the expression of VEGF, MMP-9, the activity of COX-2 and stimulates the apoptosis in eutopic, ectopic endometrial stromal cells of women with endometriosis].

OBJECTIVE: To investigate the effect of targeted interruption of cyclooxygenase-2 (COX-2) gene by small interference RNA (siRNA) on the expression of COX-2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in eutopic and ectopic endometrial stromal cells (ESC) with endometriosis, and the effect on the content of 6-keto-prostaglandin-F1α (6-keto-PGF1α, metabolites of COX) and the apoptosis of eutopic and ectopic ESC with endometriosis. METHODS: Ectopic and eutopic ESC from 30 women with endometriosis were isolated and cultured respectively. Then, ESC were classified into three groups: interference group, negative control group and blank control group. ESC in interference group were injected into siRNA transfection complex while ESC in negative control group were injected into negative control transfection complex. ESC from 10 participants without endometriosis were the normal control group. The mRNA and protein expression of COX-2, VEGF, MMP-9 in pre-transfected and post-transfected eutopic and ectopic ESC were detected through real time reverse transcription PCR and western blot. The content of 6-keto-PGF1α was determined by ELISA, the apoptotic cells were detected by flow cytometry. RESULTS: After interruption of COX-2 gene, there were no significant difference in the mRNA and protein expression of COX-2, VEGF and MMP-9 between the negative control group and blank control group (P > 0.05); the mRNA and protein expression of the three genes in interference group were significantly lower than those in negative control group and blank control group (P < 0.05); the mRNA expression of the three genes in interference group of eutopic ESC were 0.87 ± 0.06, 1.76 ± 0.59, 1.04 ± 0.32, in interference group of ectopic ESC were 0.75 ± 0.12, 1.62 ± 0.47, 0.88 ± 0.25, the protein expression of the three genes in interference group of eutopic ESC were 0.457 ± 0.019, 0.500 ± 0.012, 0.361 ± 0.008, in interference group of ectopic ESC were 0.323 ± 0.018, 0.474 ± 0.016, 0.339 ± 0.009; the mRNA and protein expression of the three genes in ectopic ESC had a more reduction than those in eutopic ESC (P < 0.05). The results from ELISA revealed that the content of 6-keto-PGF1α in the normal control group [(17.7 ± 1.9) pg/ml] were significantly lower than those in the blank control group (P < 0.05), the content of 6-keto-PGF1α in ectopic ESC were significantly higher than that in eutopic ESC (P < 0.05), the content of 6-keto-PGF1α in the blank control group of eutopic and ectopic ESC were (32.4 ± 2.6) pg/ml, (38.2 ± 3.7) pg/ml; there was no significant difference in the content of 6-keto-PGF1α between the negative control group and blank control group (P > 0.05); compared with those of negative control group and blank control group, the content of 6-keto-PGF1α in interference group decreased significantly (P < 0.05), the content of 6-keto-PGF1α in interference group of eutopic and ectopic ESC were (17.1 ± 2.4) pg/ml, (20.9 ± 2.7) pg/ml; the content of 6-keto-PGF1α in eutopic ESC had a slightly more reduction than that in ectopic ESC (P > 0.05). The results from flow cytometry displayed that, there was no significant difference in apoptotic cells between the negative control group and blank control group (P > 0.05); compared with those of negative control group and blank control group, more apoptotic cells were detected in interference group and the difference was significant (P < 0.01); the apoptotic cells in ectopic ESC were significantly more than that in eutopic ESC (P < 0.05); the apoptosis rate in interference group of eutopic and ectopic ESC were (33.76 ± 0.06)%, (47.18 ± 0.12)%. CONCLUSIONS: Our results suggested the targeted interruption of COX-2 gene by siRNA effectively inhibited the mRNA and protein expression of COX-2, VEGF and MMP-9 in both eutopic ESC and ectopic ESC with endometriosis, greatly increased the apoptotic rate of cells and obviously reduced the content of 6-keto-PGF1α by inhibiting the activity of COX-2. And the changes in ectopic endometrium were more evident than those in eutopic endometrium.

Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus.

Clinical studies have demonstrated that conditionally replicating adenovirus is safe. We constructed an oncolytic adenovirus, Ad-hTERT-E1a-Apoptin, using a cancer-specific promoter (human telomerase reverse transcriptase promoter, hTERTp) and a cancer cell-selective apoptosis-inducing gene (Apoptin). Ad-hTERT-E1a-Apoptin was proven effective both in vitro and in vivo in our previous study. In this study, the preclinical safety profiles of Ad-hTERT-E1a-Apoptin in animal models were investigated. At doses of 5.0×10(8), 2.5×10(9), and 1.25×10(10) viral particles (VP)/kg, Ad-hTERT-E1a-Apoptin had no adverse effects on mouse behavior, muscle cooperation, sedative effect, digestive system, and nervous systems, or on beagle cardiovascular and respiratory systems at 5.0×10(8), 2.5×10(9), and 1.25×10(10) VP/kg doses. In acute toxicity tests in mice, the maximum tolerated dose>5×10(10) VP/kg. There was no inflammation or ulceration at the injection sites within two weeks. In repeat-dose toxicological studies, the no observable adverse effect levels of Ad-hTERT-E1a-Apoptin in rats (1.25×10(10) VP/kg) and beagles (2.5×10(9) VP/kg) were 62.5- and 12.5-fold of the proposed clinical dose, respectively. The anti-virus antibody was produced in animal sera. Bone marrow examination revealed no histopathological changes. Guinea pigs sensitized by three repeated intraperitoneal injections of 1.35×10(10) VP/mL Ad-hTERT-E1a-Apoptin each and challenged by one intravenous injection of 1.67×10(8) VP/kg Ad-hTERT-E1a-Apoptin did not exhibit any sign of systemic anaphylaxis. Our data from different animal models suggest that Ad-hTERT-E1a-Apoptin is a safe anti-tumor therapeutic agent.

Association of systemic inflammation index with psoriasis risk and psoriasis severity: A retrospective cohort study of NHANES 2009 to 2014.

To investigate the association of systemic inflammation index (SII) with psoriasis risk and psoriasis severity. This is a retrospective cohort study based on data from the National Health and Nutrition Examination Survey database from 2009 to 2014. The psoriasis information was obtained from the questionnaire data, and the SII was calculated as neutrophil × platelet/lymphocyte. We performed matching by controlling age and gender to reach a 1:2 ratio for better statistical power. Weighted logistic regression analysis, subgroup analysis, restricted cubic spline analysis, and threshold analysis were used to evaluate the association of SII with psoriasis risk. Besides, mediation analysis was conducted to assess the possible regulatory path. Finally, the receiver operating characteristic curve was plotted to analyze the predictive value of SII for psoriasis severity. The study involved 16,466 participants including 16,020 no-psoriasis participants and 446 psoriasis participants. After matching, psoriasis and non-psoriasis individuals were 446 and 892, respectively. SII was significantly higher in the psoriasis group than the non-psoriasis group (P < .05). Additionally, white blood cells and monocytes were significantly linked to psoriasis risk and SII scores (P < .05). Besides, SII elevation was an independent predictor for upregulated psoriasis risk (P < .05). There was a nonlinear relationship between SII and psoriasis risk (P nonlinear < .05), which was not mediated by white blood cells and monocytes. Unexpectedly, SII had no significance in predicting SII severity (P > .05). SII can independently predict psoriasis risk but has no impact on psoriasis severity. Further, SII serves as a potential and robust biomarker for identifying high-risk psoriasis individuals.

Construction of heterogeneously connected cobalt-based MOF-COF and its application in highly selective separation of trace lead ions.

As a new type of porous crystalline composite material, MOF-COF has shown great advantages in metal separation. Herein, a CoMOF-COF was designed for highly selective separation of trace Pb2+ ions. The designed CoMOF-COF has a high density of nitrogen-oxygen functional groups and can selectively separate metal ions. There is a strong affinity between the designed CoMOF-COF material and metal Pb2+ ions, which can be attributed to the ordered heterogeneous porous structure and large amounts of nitrogen-and oxygen-containing functional groups. The composite showed high adsorption selectivity for Pb2+ ions and had adsorption capacity of 33 mg g-1, with high chemical stability. Based on this solid phase extraction material, a high sensitivity detection method for Pb2+ ions was established, which has the detection limit of 37.3 ng L-1, precision of 1.9 %. Linear detection range is 0.2-10 ng mL-1, and the detection of Pb2+ ions in actual water samples was realized. Through this study, it is proved that the strong affinity between the designed CoMOF-COF materials and metal Pb2+ ions can be attributed to the soft and hard acid-base theory, which reveals the structure-activity relationship between the porous heterostructure of such materials and metal separation, providing a highly selective separation material for the separation of other environmental pollutants.

Realizing Ultrahigh Cycle Life Anode for Sodium-Ion Batteries through Heterostructure Design and Introducing Electro Active Polymer Coating.

Bi2S3 has attracted increasing attention in sodium-ion batteries (SIBs) for its high theoretical capacity and low discharge platform. However, the sodium storage performance of Bi2S3 is limited by poor electrical conductivity and volume expansion during cycling. Herein, we report a special polypyrrole (PPy)-coated MoS2/Bi2S3 (MBS@PPy) heterostructure composite obtained by hydrothermal reaction as an anode material for SIB. As a result, the MBS@PPy composites demonstrate exceptional electrochemical performance in SIB, exhibiting a high capacity of 361.1 mA h g-1 at 10 A g-1 and showcasing remarkable rate performance. Even under a high current density of 35 A g-1, the specific capacity remains stable at 280 mA h g-1 after 2,000 cycles. Furthermore, a successfully assembled Na3V2(PO4)3//MBS@PPy sodium-ion full cell can achieve an impressive specific capacity of approximately 400 mA h g-1 after 300 cycles at 0.5 A g-1. In MBS@PPy composites, the polypyridine coating not only improves the interfacial conductivity of nanorods but also effectively inhibits the agglomeration between nanorods due to large volume changes. The MoS2 heterostructure further inhibits the coarsening of the internal structure, improves electron transport and reaction kinetics, and increases the rate capability of the material. This work provides an effective strategy to develop energy storage materials with superior electrochemical properties.

Organocatalytic Atroposelective Construction of Pentatomic Heterobiaryl Diamines through Arylation of 5-Aminoisoxazoles with Azonaphthalenes.

An efficient catalytic asymmetric Michael-type reaction of azonaphthalenes with 5-aminoisoxazoles has been developed. The reaction was based on the utilization of a chiral phosphoric acid as the catalyst, delivering a large panel of axially chiral heterobiaryl diamines in generally good yields with excellent enantioselectivities. The gram-scale reaction and postmodification of the chiral product demonstrated their potentials in the synthesis of chiral catalysts and ligands. This approach not only provides a useful method for the construction of pentatomic heterobiaryl scaffolds but also offers new members to the axially chiral diamine family with promising applications in synthetic and medicinal chemistry.

IL-23 inhibitor enhances the effects of PTEN DNA-loaded lipid nanoparticles for metastatic CRPC therapy.

Introduction: Metastatic castration-resistant prostate cancer (mCRPC) patients face challenges due to limited treatment options. About 50% of patients with mCRPC have a functional loss of phosphatase and tensin homology deleted on chromosome 10 (PTEN), leading to tumor progression, metastasis, and immune suppression. Moreover, elevated IL-23 produced by myeloid-derived suppressor cells (MDSCs) is found in CRPC patients, driving tumor progression. Therefore, a combination strategy based on PTEN restoration and IL-23 inhibition may block CRPC progression and metastasis. Methods: The antitumor effect of restoring PTEN expression combined with the IL-23 inhibitor Apilimod was studied in a mouse model of bone metastasis CRPC and mouse prostate cancer RM-1 cells. To verify the targeting ability of PTEN DNA coated with lipid nanoparticles (LNP@PTEN) in vitro and in vivo. In addition, RT-qPCR and flow cytometry were used to investigate the related mechanisms of the antitumor effect of LNP@PTEN combined with Apilimod. Results: LNPs exhibited significant tumor-targeting and tumor accumulation capabilities both in vitro and in vivo, enhancing PTEN expression and therapeutic efficacy. Additionally, the combination of LNP@PTEN with the IL-23 inhibitor Apilimod demonstrated enhanced inhibition of tumor growth, invasion, and metastasis (particularly secondary organ metastasis) compared to other groups, and extended the survival of mice to 41 days, providing a degree of bone protection. These effects may be attributed to the PTEN function restoration combined with IL-23 inhibition, which help reverse immune suppression in the tumor microenvironment by reducing MDSCs recruitment and increasing the CD8+/CD4+ T cell ratio. Discussion: In summary, these findings highlight the potential of LNPs for delivering gene therapeutic agents. And the combination of LNP@PTEN with Apilimod could achieve anti-tumor effects and improve tumor microenvironment. This combinational strategy opens new avenues for the treatment of mCRPC.

A Study on AIDS Self-Management Status and Its Influencing Factors.

Purpose: To investigate and analyse the status quo of the self-management of patients living with HIV/AIDS (PLWHA) and its influencing factors and to provide the basis for formulating intervention strategies. Methods: In this cross-sectional study, 300 PLWHA who visited the Infection Center of Beijing Youan Hospital, Capital Medical University between September 2021 and December 2021 were enrolled using the convenience sampling method. Demographic characteristics and disease-related data were collected for each participant. The HIV/AIDS Self-Management Scale was used to evaluate the self-management ability of PLWHA. Results: A total of 251 male and 49 female PLWHA were included in this study, with an average age of 39.08 ± 12.09 years and an average disease duration of 9.61 ± 37.04 months. Univariate analysis showed that the PLWHA's place of residence, educational level, physical condition, family relations, duration of HIV disease, receipt or not of antiviral therapy and knowledge of disease had an influence on the scores of the HIV Self-Management Scale (all p < 0.05). The results of the self-management scores indicated that the total score for self-management was 41.5 ± 6.4 points, with a scoring rate of 69.6%, which was at a medium level. Long-term self-management had the highest scoring rate (12.2 ± 2.5 points), followed by daily health management (22.3 ± 4.3 points), and social support for self-management had the lowest scoring (5.1 ± 0.9 points). Multivariable analysis showed that the self-management ability of PLWHA was related to educational level, duration of disease and family relations (R2 = 0.67, F = 121.7, p < 0.05). Conclusion: The self-management level of patients with AIDS, especially the social support of daily health management and self-management, needs to be further improved. Educational level, duration of disease and family relations are important factors influencing the self-management of PLWHA.

Disruption of maternal vascular remodeling by a fetal endoretrovirus-derived gene in preeclampsia.

BACKGROUND: Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. RESULTS: By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. CONCLUSIONS: Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal-fetal interface formation.