Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis.

Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expanding the accessibility of CAR-T therapy, whereas the risks of allograft rejection have hampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treated one patient with refractory immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis with these cells. This study was registered at ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving complete B cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients, primarily shown by the significant improvement in the clinical response index scores for the two diseases, respectively, and supported by the observations of reversal of inflammation and fibrosis. Our results demonstrate the high safety and promising immune modulatory effect of the off-the-shelf CAR-T cells in treating severe refractory autoimmune diseases.

Publisher Correction: K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8+ T cell activation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Strong yet ductile nanolamellar high-entropy alloys by additive manufacturing.

Additive manufacturing produces net-shaped components layer by layer for engineering applications1-7. The additive manufacture of metal alloys by laser powder bed fusion (L-PBF) involves large temperature gradients and rapid cooling2,6, which enables microstructural refinement at the nanoscale to achieve high strength. However, high-strength nanostructured alloys produced by laser additive manufacturing often have limited ductility3. Here we use L-PBF to print dual-phase nanolamellar high-entropy alloys (HEAs) of AlCoCrFeNi2.1 that exhibit a combination of a high yield strength of about 1.3 gigapascals and a large uniform elongation of about 14 per cent, which surpasses those of other state-of-the-art additively manufactured metal alloys. The high yield strength stems from the strong strengthening effects of the dual-phase structures that consist of alternating face-centred cubic and body-centred cubic nanolamellae; the body-centred cubic nanolamellae exhibit higher strengths and higher hardening rates than the face-centred cubic nanolamellae. The large tensile ductility arises owing to the high work-hardening capability of the as-printed hierarchical microstructures in the form of dual-phase nanolamellae embedded in microscale eutectic colonies, which have nearly random orientations to promote isotropic mechanical properties. The mechanistic insights into the deformation behaviour of additively manufactured HEAs have broad implications for the development of hierarchical, dual- and multi-phase, nanostructured alloys with exceptional mechanical properties.

Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.

BACKGROUND: Daratumumab, a monoclonal antibody targeting CD38, has been approved for use with standard myeloma regimens. An evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients with newly diagnosed multiple myeloma is needed. METHODS: In this phase 3 trial, we randomly assigned 709 transplantation-eligible patients with newly diagnosed multiple myeloma to receive either subcutaneous daratumumab combined with VRd induction and consolidation therapy and with lenalidomide maintenance therapy (D-VRd group) or VRd induction and consolidation therapy and lenalidomide maintenance therapy alone (VRd group). The primary end point was progression-free survival. Key secondary end points were a complete response or better and minimal residual disease (MRD)-negative status. RESULTS: At a median follow-up of 47.5 months, the risk of disease progression or death in the D-VRd group was lower than the risk in the VRd group. The estimated percentage of patients with progression-free survival at 48 months was 84.3% in the D-VRd group and 67.7% in the VRd group (hazard ratio for disease progression or death, 0.42; 95% confidence interval, 0.30 to 0.59; P<0.001); the P value crossed the prespecified stopping boundary (P = 0.0126). The percentage of patients with a complete response or better was higher in the D-VRd group than in the VRd group (87.9% vs. 70.1%, P<0.001), as was the percentage of patients with MRD-negative status (75.2% vs. 47.5%, P<0.001). Death occurred in 34 patients in the D-VRd group and 44 patients in the VRd group. Grade 3 or 4 adverse events occurred in most patients in both groups; the most common were neutropenia (62.1% with D-VRd and 51.0% with VRd) and thrombocytopenia (29.1% and 17.3%, respectively). Serious adverse events occurred in 57.0% of the patients in the D-VRd group and 49.3% of those in the VRd group. CONCLUSIONS: The addition of subcutaneous daratumumab to VRd induction and consolidation therapy and to lenalidomide maintenance therapy conferred a significant benefit with respect to progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma. (Funded by the European Myeloma Network in collaboration with Janssen Research and Development; PERSEUS ClinicalTrials.gov number, NCT03710603; EudraCT number, 2018-002992-16.).

K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8(+) T cell activation.

The key molecular mechanisms that control signaling via T cell antigen receptors (TCRs) remain to be fully elucidated. Here we found that Nrdp1, a ring finger-type E3 ligase, mediated Lys33 (K33)-linked polyubiquitination of the signaling kinase Zap70 and promoted the dephosphorylation of Zap70 by the acidic phosphatase-like proteins Sts1 and Sts2 and thereby terminated early TCR signaling in CD8(+) T cells. Nrdp1 deficiency significantly promoted the activation of naive CD8(+) T cells but not that of naive CD4(+) T cells after engagement of the TCR. Nrdp1 interacted with Zap70 and with Sts1 and Sts2 and connected K33 linkage of Zap70 to Sts1- and Sts2-mediated dephosphorylation. Our study suggests that Nrdp1 terminates early TCR signaling by inactivating Zap70 and provides new mechanistic insights into the non-proteolytic regulation of TCR signaling by E3 ligases.

Tumor-polarized GPX3+ AT2 lung epithelial cells promote premetastatic niche formation.

The cellular and molecular components required for the formation of premetastatic niche (PMN) to promote lung metastasis need to be further investigated. Lung epithelial cells have been reported to exhibit immunomodulatory roles in lung homeostasis and also to mediate immunosuppressive PMN formation in lung metastasis. Here, by single-cell sequencing, we identified a tumor-polarized subpopulation of alveolar type 2 (AT2) epithelial cells with increased expression of glutathione peroxidase 3 (GPX3) and high production of interleukin (IL)-10 in the PMN. IL-10-producing GPX3+ AT2 cells inhibited CD4+ T cell proliferation but enhanced regulatory T cell generation. Mechanistically, tumor exosome-inducing GPX3 expression is required for GPX3+ AT2 cells to preferentially produce IL-10 by stabilizing hypoxia-inducible factor 1 (HIF-1α) and promoting HIF-1α-induced IL-10 production. Accordingly, conditional knockout of GPX3 in AT2 cells suppressed lung metastasis in spontaneous metastatic models. Together, our findings reveal a role of tumor-polarized GPX3+ AT2 cells in promoting lung PMN formation, adding insights into immune evasion in lung metastasis and providing potential targets for the intervention of tumor metastasis.

van der Waals Integration of Large-Area Monocrystalline 3D Perovskite Thin Films on Arbitrary Semiconductor Substrates for Heterojunctions.

Perovskite monocrystalline films are regarded as desirable candidates for the integration of high-performance optoelectronics due to their unique photophysical properties. However, the heterogeneous integration of a perovskite monocrystalline film with other semiconductors is fundamentally limited by the lattice mismatch, which hinders direct epitaxy. Herein, the van der Waals (vdW) integration strategy for 3D perovskites is developed, where perovskite monocrystalline films are epitaxially grown on the mother substrate, followed by its peeling off and transferring to arbitrary semiconductors, forming monocrystalline heterojunctions. The as-achieved CsPbBr3-Nb-doped SrTiO3 (Nb:STO) vdW p-n heterojunction exhibited comparable performance to their directly epitaxial counterpart, demonstrating the feasibility of vdW integration for 3D perovskites. Furthermore, the vdW integration could be extended to silicon substrates, rendering the CsPbBr3-n-Si and CsPbCl3-p-Si p-n heterojunction with apparent rectification behaviors and photoresponse. The vdW integration significantly enriches the selections of semiconductors hybridizing with perovskites and provides opportunities for monocrystalline perovskite optoelectronics with complex configurations and multiple functionalities.

Joint application of A-InDels and miniSTRs for forensic personal, full and half sibling identifications, and genetic differentiation analyses in two populations from China.

BACKGROUND: Previously, a novel multiplex system of 64 loci was constructed based on capillary electrophoresis platform, including 59 autosomal insertion/deletions (A-InDels), two Y-chromosome InDels, two mini short tandem repeats (miniSTRs), and an Amelogenin gene. The aim of this study is to evaluate the efficiencies of this multiplex system for individual identification, paternity testing and biogeographic ancestry inference in Chinese Hezhou Han (CHH) and Hubei Tujia (CTH) groups, providing valuable insights for forensic anthropology and population genetics research. RESULTS: The cumulative values of power of discrimination (CDP) and probability of exclusion (CPE) for the 59 A-InDels and two miniSTRs were 0.99999999999999999999999999754, 0.99999905; and 0.99999999999999999999999999998, 0.99999898 in CTH and CHH groups, respectively. When the likelihood ratio thresholds were set to 1 or 10, more than 95% of the full sibling pairs could be identified from unrelated individual pairs, and the false positive rates were less than 1.2% in both CTH and CHH groups. Biogeographic ancestry inference models based on 35 populations were constructed with three algorithms: random forest, adaptive boosting and extreme gradient boosting, and then 10-fold cross-validation analyses were applied to test these three models with the average accuracies of 86.59%, 84.22% and 87.80%, respectively. In addition, we also investigated the genetic relationships between the two studied groups with 33 reference populations using population statistical methods of FST, DA, phylogenetic tree, PCA, STRUCTURE and TreeMix analyses. The present results showed that compared to other continental populations, the CTH and CHH groups had closer genetic affinities to East Asian populations. CONCLUSIONS: This novel multiplex system has high CDP and CPE in CTH and CHH groups, which can be used as a powerful tool for individual identification and paternity testing. According to various genetic analysis methods, the genetic structures of CTH and CHH groups are relatively similar to the reference East Asian populations.

Oral Hypoxia-Inducible Factor 2α Inhibitor Belzutifan in Ocular von Hippel-Lindau Disease: Subgroup Analysis of the Single-Arm Phase 2 LITESPARK-004 Study.

PURPOSE: To report the efficacy of the oral hypoxia-inducible factor 2α inhibitor belzutifan in participants with von Hippel-Lindau disease-associated retinal hemangioblastomas in the LITESPARK-004 study. DESIGN: Subgroup analysis of the phase 2, single-arm, open-label LITESPARK-004 study. PARTICIPANTS: Adults with 1 or more von Hippel-Lindau disease-associated measurable renal cell carcinoma tumors not requiring immediate surgical intervention were eligible. METHODS: Participants received oral belzutifan 120 mg once daily until disease progression or unacceptable treatment-related toxicity. MAIN OUTCOME MEASURES: Efficacy of belzutifan in retinal hemangioblastomas was a secondary end point, measured as response (improved, stable, or progressed) by independent reading center-certified graders based on color fundus imaging performed every 12 weeks using the investigator's preferred imaging standards. Additional assessments, where available, included OCT and ultra-widefield fluorescein angiography. RESULTS: Among 61 participants in LITESPARK-004, 12 had 1 or more evaluable active retinal hemangioblastomas in 16 eyes at baseline per independent reading center. As of April 1, 2022, the median follow-up for participants with ocular von Hippel-Lindau disease at baseline was 37.3 months. All 16 eyes were graded as improved, with a response rate of 100.0% (95% confidence interval, 79.4%-100%). No new retinal hemangioblastomas or ocular disease progression were reported as of data cutoff date. Eight participants underwent additional multimodal eye assessments performed at the National Institutes of Health study site. Among this subgroup, 10 of 24 hemangioblastomas in 8 eyes of 6 participants measured 500 µm or more in greatest linear dimension at baseline and were analyzed further. All 10 hemangioblastomas had a mean area reduction of 15% or more by month 12 and of 30% or more by month 24. CONCLUSIONS: Belzutifan showed promising activity against ocular von Hippel-Lindau disease, including capacity to control retinal hemangioblastomas, with effects sustained for more than 2 years while treatment is ongoing. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Autosis: a new form of cell death in myocardial ischemia-reperfusion injury.

Cardiomyocytes undergo a variety of cell death events during myocardial ischemia‒reperfusion injury (MIRI). Understanding the causes of cardiomyocyte mortality is critical for the prevention and treatment of MIRI. Among the various types of cell death, autosis is a recently identified type of autophagic cell death with distinct morphological and chemical characteristics. Autosis can be attenuated by autophagy inhibitors but not reversed by apoptosis or necrosis inhibitors. In recent years, it has been shown that during the late phase of reperfusion, autosis is activated, which exacerbates myocardial injury. This article describes the characteristics of autosis, autophagic cell death, and the relationship between autophagic cell death and autosis; reviews the mechanism of autosis in MIRI; and discusses its clinical significance.

CircOGDH Is a Penumbra Biomarker and Therapeutic Target in Acute Ischemic Stroke.

BACKGROUND: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Prediction of penumbra existence after AIS is crucial for making decision on reperfusion therapy. Yet a fast, inexpensive, simple, and noninvasive predictive biomarker for the poststroke penumbra with clinical translational potential is still lacking. We aim to investigate whether the CircOGDH (circular RNA derived from oxoglutarate dehydrogenase) is a potential biomarker for penumbra in patients with AIS and its role in ischemic neuronal damage. METHODS: CircOGDH was screened from penumbra of middle cerebral artery occlusion mice and was assessed in plasma of patients with AIS by quantitative polymerase chain reaction. Magnetic resonance imaging was used to examine the penumbra volumes. CircOGDH interacted with miR-5112 (microRNA-5112) in primary cortical neurons was detected by fluorescence in situ hybridization, RNA immunoprecipitation, and luciferase reporter assay. Adenovirus-mediated CircOGDH knockdown ameliorated neuronal apoptosis induced by COL4A4 (Gallus collagen, type IV, alpha IV) overexpression. Transmission electron microscope, nanoparticle tracking analysis, and Western blot were performed to confirm exosomes. RESULTS: CircOGDH expression was dramatically and selectively upregulated in the penumbra tissue of middle cerebral artery occlusion mice and in the plasma of 45 patients with AIS showing a 54-fold enhancement versus noncerebrovascular disease controls. Partial regression analysis revealed that CircOGDH expression was positively correlated with the size of penumbra in patients with AIS. Sequestering of miR-5112 by CircOGDH enhanced COL4A4 expression to elevate neuron damage. Additionally, knockdown of CircOGDH significantly enhanced neuronal cell viability under ischemic conditions. Furthermore, the expression of CircOGDH in brain tissue was closely related to that in the serum of middle cerebral artery occlusion mice. Finally, we found that CircOGDH was highly expressed in plasma exosomes of patients with AIS compared with those in noncerebrovascular disease individuals. CONCLUSIONS: These results demonstrate that CircOGDH is a potential therapeutic target for regulating ischemia neuronal viability, and is enriched in neuron-derived exosomes in the peripheral blood, exhibiting a predictive biomarker of penumbra in patients with AIS.

cFLIPL alleviates myocardial ischemia-reperfusion injury by regulating pyroptosis.

Alleviating myocardial ischemia-reperfusion injury (MIRI) plays a critical role in the prognosis and improvement of cardiac function following acute myocardial infarction. Pyroptosis is a newly identified form of cell death that has been implicated in the regulation of MIRI. In our study, H9c2 cells and SD rats were transfected using a recombinant adenovirus vector carrying cFLIPL , and the transfection was conducted for 3 days. Subsequently, H9c2 cells were subjected to 4 h of hypoxia followed by 12 h of reoxygenation to simulate an in vitro ischemia-reperfusion model. SD rats underwent 30 min of ischemia followed by 2 h of reperfusion to establish an MIRI model. Our findings revealed a notable decrease in cFLIPL expression in response to ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R) injuries. Overexpression of cFLIPL can inhibit pyroptosis, reducing myocardial infarction area in vivo, and enhancing H9c2 cell viability in vitro. I/R and H/R injuries induced the upregulation of ASC, cleaved Caspase 1, NLRP3, GSDMD-N, IL-1ß, and IL-18 proteins, promoting cell apoptosis. Our research indicates that cFLIPL may suppress pyroptosis by strategically binding with Caspase 1, inhibiting the release of inflammatory cytokines and preventing cell membrane rupture. Therefore, cFLIPL could potentially serve as a promising target for alleviating MIRI by suppressing the pyroptotic pathway.

Sea Cucumber Viscera Contains Novel Non-Holostane-Type Glycoside Toxins that Possess a Putative Chemical Defense Function.

Sea cucumbers frequently expel their guts in response to predators and an aversive environment, a behavior perceived as releasing repellents involved in chemical defense mechanisms. To investigate the chemical nature of the repellent, the viscera of stressed sea cucumbers (Apostichopus japonicus) in the Yellow Sea of China were collected and chemically analyzed. Two novel non-holostane triterpene glycosides were isolated, and the chemical structures were elucidated as 3ꞵ-O-[ꞵ-D-glucopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (1) and 3ꞵ-O-[ꞵ-D-quinovopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (2) by spectroscopic and mass-spectrometric analyses, exemplifying a triterpene glycoside constituent of an oligosaccharide containing two sugar-units and a non-holostane aglycone. Zebrafish embryos were exposed to various doses of 1 and 2 from 4 to 96 hpf. Compound 1 exposure showed 96 h-LC50 41.5 µM and an increased zebrafish mortality rates in roughly in a dose- and time-dependent manner. Compound 2, with different sugar substitution, exhibited no mortality and moderate teratogenic toxicity with a 96 h-EC50 of 173.5 µM. Zebrafish embryos exhibited teratogenic effects, such as reduced hatchability and total body length. The study found that triterpene saponin from A. japonicus viscera had acute toxicity in zebrafish embryos, indicating a potential chemical defense role in the marine ecosystem.

Label-free cell phenotypic profiling of histamine H4R receptor and discovery of non-competitive H4R antagonist from natural products.

Histamine 4 receptor (H4R), the most recently identified subtype of histamine receptor, primarily induces inflammatory reactions upon activation. Several H4R antagonists have been developed for the treatment of inflammatory bowel disease (IBD) and atopic dermatitis (AD), but their use has been limited by adverse side effects, such as a short half-life and toxicity. Natural products, as an important source of anti-inflammatory agents, offer minimal side effects and reduced toxicity. This work aimed to identify novel H4R antagonists from natural products. An H4R target-pathway model deconvoluted downstream Gi and MAPK signaling pathways was established utilizing cellular label-free integrative pharmacology (CLIP), on which 148 natural products were screened. Cryptotanshinone was identified as selective H4R antagonist, with an IC50 value of 11.68 ± 1.30 µM, which was verified with Fluorescence Imaging Plate Reader (FLIPR) and Cellular Thermal Shift (CTS) assays. The kinetic binding profile revealed the noncompetitive antagonistic property of cryptotanshinone. Two allosteric binding sites of H4R were predicted using SiteMap, Fpocket and CavityPlus. Subsequent molecular docking and dynamics simulation indicated that cryptotanshinone interacts with H4R at a pocket formed by the outward interfaces between TM3/4/5, potentially representing a new allosteric binding site for H4R. Overall, this study introduced cryptotanshinone as a novel H4R antagonist, offering promise as a new hit for drug design of H4R antagonist. Additionally, this study provided a novel screening model for the discovery of H4R antagonists.

Spatio-temporal dynamics and socio-ecological determinants of ecosystem service interplays in Shandong Province's coastal region (2000-2020): Implications for environmental protection and sustainable ecosystem management.

The sustainable management of multiple concurrent ecosystem services (ESs) requires a comprehensive understanding of the interconnections between various ESs. In this study, we develop spatial maps for six distinct ESs using a variety of models, and we quantify their trade-offs, synergies, and bundling patterns through spatial mapping and statistical methodologies. We further delve into the antagonistic and synergistic dynamics between different ESs within each Ecosystem Service Bundle (ESB), and employ GeoDetector to pinpoint the key drivers of each ES. Our findings reveal that: (1) The spatial distributions of ESs are heterogeneous, with most ESs exhibiting a downward trend except for GP and SC, which are on the rise. CS shows positive correlations with all other five ES indicators. HQ exhibits positive correlations with SC and RS, whereas negative correlations are observed between HQ-GP and WC-RS. Six ES pairs demonstrate a decline in synergistic relationships, but an increase in trade-off relationships. (2) We distinguish six types of ESBs, each differing in their combination and extent of ES provision. The trade-offs and synergies within these distinct ESBs display both commonalities and differences. In certain ESBs, supply services display synergistic relationships with other ESs. We leverage ES bundles as the foundation for studying spatial planning zoning, revealing a diversity in the interactions between different ES pairs and the driving factors of ES. Therefore, we establish the theoretical basis for formulating spatial planning on the interrelationships and drivers of ES under spatial and temporal changes. We anticipate that our findings will offer valuable scientific insight for the development of future ecological conservation and spatial planning strategies in the region.

Effects of rhythm-control and rate-control strategies on cognitive function and dementia in atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Growing evidence suggests that atrial fibrillation (AF) is an independent risk factor for cognitive impairment and dementia, even in the absence of thromboembolic events and stroke. Whether rhythm-control therapy can protect cognitive function remains unclear. We aimed to evaluate the efficacy of rhythm-control strategies in patients with AF regarding cognitive function and dementia risk. METHODS: We systematically searched the PubMed, Embase and Cochrane Library databases for randomised clinical trials, cohort and case-control studies evaluating the associations between rhythm-control strategies and cognitive function outcomes up to May 2023. We assessed the risk of bias using the ROBINS-I and the Cochrane risk-of-bias tool. Both fixed- and random-effects models were used to create summary estimates of risk. RESULTS: We included a total of 14 studies involving 193,830 AF patients. In the pooled analysis, compared with rate-control, rhythm-control therapy was significantly associated with a lower risk of future dementia (hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.62-0.89; I2 = 62%). Among the rhythm-control strategies, AF ablation is a promising treatment that was related to significantly lower risks of overall dementia (HR 0.62; 95% CI 0.56-0.68; I2 = 42%), Alzheimer's disease (HR 0.78; 95% CI 0.66-0.92; I2 = 0%) and vascular dementia (HR 0.58; 95% CI 0.42-0.80; I2 = 31%). Pooled results also showed that compared with patients without ablation, those who underwent AF ablation had significantly greater improvement in cognitive score (standardized mean difference (SMD) 0.85; 95% CI 0.30-1.40; P = 0.005; I2 = 76%). CONCLUSIONS: Rhythm-control strategies, especially ablation, are effective in protecting cognitive function, reducing dementia risk and thus improving quality of life in AF patients.

Effect of intravenous anesthetic drugs on fertilization rate in oocyte retrieval.

BACKGROUND: The purpose of this study was to investigate the effects of intravenous anesthetic drugs on fertilization rate in subjects receiving oocyte retrieval by assisted reproduction technology (ART). METHODS: A retrospective cohort study was designed. The clinical information of subjects who received oocyte retrieval procedure was collected. The subjects were divided into two groups based on the type of anesthesia used: the no-anesthesia group and the intravenous anesthesia group. Propensity score matching (PSM) was performed and multiple linear regression analyses were conducted. Fertilization rate was compared between the two groups before and after PSM. RESULTS: A total of 765 subjects were divided into two groups: the no-anesthesia group (n = 482) and the intravenous anesthesia group (n = 283). According to propensity scores, 258 pairs of subjects were well matched, and the baseline data between the two groups were not significantly different (P > 0.05). Fertilization rate was 77% in the intravenous anesthesia group, and 76% in the no-anesthesia group, without significant between-group difference (P = 0.685). Before matching, Poisson regression analysis showed no effect of intravenous anesthetic drugs on fertilization rate (RR = 0.859, 95%CI: 0.59 to 1.25, P = 0.422). After matching, no difference was found either (RR = 0.935, 95%CI: 0.67 to 1.29, P = 0.618). CONCLUSION: Intravenous anesthetic drugs may exert no effects on fertilization rate in subjects receiving ART.

Protective mechanism of Paeonol on central nervous system.

Cerebrovascular diseases involve neuronal damage, resulting in degenerative neuropathy and posing a serious threat to human health. The discovery of effective drug components from natural plants and the study of their mechanism are a research idea different from chemical synthetic medicines. Paeonol is the main active component of traditional Chinese medicine Paeonia lactiflora Pall. It widely exists in many medicinal plants and has pharmacological effects such as anti-atherosclerosis, antiplatelet aggregation, anti-oxidation, and anti-inflammatory, which keeps generally used in the treatment of cardiovascular and cerebrovascular diseases. Based on the therapeutic effects of Paeonol for cardiovascular and cerebrovascular diseases, this article reviewed the pharmacological effects of Paeonol in Alzheimer's disease, Parkinson's disease, stroke, epilepsy, diabetes encephalopathy, and other neurological diseases, providing a reference for the research of the mechanism of Paeonol in central nervous system diseases.

Triterpene Glycosides from the Viscera of Sea Cucumber Apostichopus japonicus with Embryotoxicity.

Sea cucumbers release chemical repellents from their guts when they are in danger from predators or a hostile environment. To investigate the chemical structure of the repellent, we collected and chemically analyzed the viscera of stressed sea cucumbers (Apostichopus japonicus) in the Yellow Sea of China. Two undescribed triterpene glycosides (1 and 2), together with a known cladoloside A (3), were identified and elucidated as 3ß-O-{2-O-[ß-d-quinovopyranosyl]-4-O-[3-O-methyl-ß-d-glucopyranosyl-(1→3)-ß-d-glucopyranosyl]-ß-d-xylopyranosyl}-holosta-9(11),25(26)-dien-16-one (1), 3ß-O-{2-O-[ß-d-glucopyranosyl]-4-O-[3-O-methyl-ß-d-glucopyranosyl-(1→3)-ß-d-glucopyranosyl]-ß-d-xylopyranosyl}-holosta-9(11),25(26)-dien-16-one (2), 3ß-O-{2-O-[3-O-methyl-ß-d-glucopyranosyl-(1→3)-ß-d-xylopyranosyl-(1→4)-ß-d-quinovopyranosyl]-ß-d-xylopyranosyl}-holosta-9(11),25(26)-dien-16-one (3) by spectroscopic analysis, including HR-ESI-MS and NMR spectra. Compounds 1, 2, and 3 display embryonic toxicity, as indicated by their 96-hour post-fertilization lethal concentration (96 hpf-LC50) values of 0.289, 0.536, and 0.091 µM, respectively. Our study discovered a class of triterpene glycoside compounds consisting of an oligosaccharide with four sugar units and a holostane aglycone. These compounds possess embryotoxicity and may serve as chemical defense molecules in marine benthic ecosystems.

Performance evaluation of an in-house panel containing 59 autosomal InDels for forensic identification in Chinese Hui and Mongolian groups.

In recent years, a novel multiplex system containing two mini-short tandem repeats, 59 autosomal InDels, two Y-chromosomal InDels, and the Amelogenin gene with all amplicons less than 200 bp has been constructed and validated by ourselves for forensic degration sample, and its forensic application efficiency has been studied in Chinese some populations. Herein, the population genetic polymorphisms of these loci were investigated in Chinese Hui (n = 249) and Mongolian (n = 222) ethnic groups using direct multiplex amplification and capillary electrophoresis platform. The forensic identification efficiencies of this self-developed system were further evaluated in these two groups. And the results showed that the values of the combined power of discrimination were 0.9999999999999999999999999999006 (Hui) and 0.999999999999999999999999999738 (Mongolian), respectively. Moreover, the combined power of exclusion values were 0.99999817 (Hui) and 0.99999779 (Mongolian). The 59 autosomal InDels used in this study exhibited high forensic identification efficiencies in 10 East Asian populations, which was also expected to be a new powerful tool for identifying degraded biological materials in East Asian populations.