CXCR4 overexpression in chronic lymphocytic leukemia associates with poorer prognosis: A prospective, single-center, observational study.

Controversial data have been reported on the prognostic value of C-X-C motif chemokine receptor 4 (CXCR4) in chronic lymphocytic leukemia (CLL). This prospective, single-center, observational study aimed to evaluate the role of CXCR4 in the pathophysiology of CLL and its prognostic role. A total of 158 patients of CLL were enrolled, and CXCR4 expression on CLL cells was detected by flow cytometry (FCM) at initial diagnosis. The patients were divided into 2 groups according to the CXCR4 mean fluorescence intensity (MFI) median. Also, four patient specimens from the CXCR4low and CXCR4high groups were selected for RNASeq analysis. The progression-free survival (PFS) of CLL patients in the CXCR4high group was significantly shorter than the CXCR4low group, with a median follow-up time of 27 months (log-rank P < 0.001). Moreover, CXCR4 overexpression (MFI > 3376) was an independent marker of poor PFS in CLL patients (P < 0.001). Analysis of RNASeq results revealed that CXCR4 plays an important role in the migration of CLL. Collectively, CXCR4 expression levels on leukemia cells can be detected rapidly by FCM. CXCR4 overexpression was significantly associated with poorer prognosis in CLL patients within a shorter follow-up time.

Maternal cardiovascular health in early pregnancy and the risk of congenital heart defects in offspring.

BACKGROUND: Congenital heart disease (CHD) is the predominant birth defect. This study aimed to explore the association between maternal cardiovascular health (CVH) and the CHD risk in offspring. METHODS: We used the prospective data from the Fujian Birth Cohort Study, collected from March 2019 to December 2022 on pregnant women within 14 weeks of gestation. Overall maternal CVH was assessed by seven CVH metrics (including physical activity, smoking, sleep duration, body mass index, blood pressure, total cholesterol, and fasting plasma glucose), with each metric classified as ideal, intermediate or poor with specific points. Participants were further allocated into high, moderate and low CVH categories based on the cumulative CVH score. The association with offspring CHD was determined with log-binominal regression models. RESULTS: A total of 19810 participants aged 29.7 (SD: 3.9) years were included, with 7846 (39.6%) classified as having high CVH, 10949 (55.3%) as having moderate CVH, and 1015 (5.1%) as having low CVH. The average offspring CHD rate was 2.52%, with rates of 2.35%, 2.52% and 3.84% across the high, moderate and low CVH categories, respectively (P = 0.02). Adjusted relative risks (RRs) of having offspring CHD were 0.64 (95% CI: 0.45-0.90, P = 0.001) for high CVH and 0.67 (95% CI: 0.48-0.93, P = 0.02) for moderate CVH compared to low CVH. For individual metrics, only ideal total cholesterol was significantly associated with lower offspring CHD (RR: 0.73, 95% CI: 0.59-0.83, P = 0.002). CONCLUSIONS: Pregnant women of high or moderate CVH categories in early pregnancy had reduced risks of CHD in offspring, compared to those of low CVH. It is important to monitor and improve CVH during pre-pregnancy counseling and early prenatal care.

Decapod iridescent virus 1 (DIV1) 168L can target cuticle protein 8 from Litopenaeus vannamei.

Decapod iridescent virus 1 (DIV1) stands as a significant pathogen affecting crustaceans, posing a grave threat to the shrimp industries in aquaculture dependent nations. Within the Iridoviridae family, the conserved envelope protein DIV1-168L plays a pivotal role in virion entry. Nonetheless, the host factors that interact with 168L remain unidentified. To address this gap, we established a cDNA library derived from Litopenaeus vannamei gill tissue and conducted yeast two-hybrid screening to identify host factors that interact with 168L. Additionally, we performed co-immunoprecipitation assays to verify the interaction between cuticle protein 8 (CP8) and 168L. Expression pattern analysis revealed the presence of CP8 transcripts in the gill and epidermis. Furthermore, immunohistochemistry results demonstrated the expression of CP8 in gill cells and its localization in the gill filament epithelium. Fluorescence analysis indicated that full-length CP8 colocalized with 168L in the cytoplasm of Sf9 cells. Removal of the signal peptide from the N-terminal of CP8 eliminated its concentration in the cytoplasm. Additionally, CP8 expression was significantly inhibited during DIV1 infection. Therefore, our research contributes to a better understanding of the entry mechanism of iridovirids. The GenBank accession number for the DIV1 sequence is MF197913.1.

Synergistic interaction between ABA and IAA due to moderate soil drying promotes grain filling of inferior spikelets in rice.

Poor grain filling of inferior spikelets is becoming a severe problem in some super rice varieties with large panicles. Moderate soil drying (MD) after pollination has been proven to be a practical strategy to promote grain filling. However, the molecular mechanisms underlying this phenomenon remain largely unexplored. Here, transcriptomic analysis of the most active grain filling stage revealed that both starch metabolism and phytohormone signaling were significantly promoted by MD treatment, accompanied by increased enzyme activities of starch synthesis and elevated abscisic acid (ABA) and indole-3-acetic acid (IAA) content in the inferior spikelet. Moreover, the IAA biosynthesis genes OsYUC11 and OsTAR2 were upregulated, while OsIAA29 and OsIAA24, which encode two repressors of auxin signaling, were downregulated by MD, implying a regulation of both IAA biosynthesis and auxin signal transduction in the inferior spikelet by MD. A notable improvement in grain filling of the inferior spikelet was found in the aba8ox2 mutant, which is mutated in an ABA catabolism gene. In contrast, overexpression of OsABA8ox2 significantly reduced grain filling. Interestingly, not only the IAA content, but also the expression of IAA biosynthesis and auxin-responsive genes displayed a similar trend to that in the inferior spikelet under MD. In addition, several OsTPP genes were downregulated in the inferior spikelets of both MD/ABA-treated wild-type plants and the aba8ox2 mutant, resulting in lower trehalose content and higher levels of -6-phosphate (T6P), thereby increasing the expression of OsTAR2, a target of T6P. Taken together, our results suggest that the synergistic interaction of ABA-mediated accumulation of IAA promotes grain filling of inferior spikelets under MD.

A convolutional neural network-based, quantitative complete blood count scattergram-mapping framework promptly screens acute promyelocytic leukemia with high sensitivity.

BACKGROUND: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by its rapidly progressive and fatal clinical course if untreated, although it is curable if treated in a timely manner. Promptly screening patients who have results that are suspicious for APL is vital to overcome early death. METHODS: The authors developed an innovative framework consisting of ResNet-18, a convolutional neural network architecture, with the objective of quantitatively mapping a complete blood count (CBC) scattergram to quickly and robustly indicate a probable susceptibility to APL. Three hundred and twenty scattergrams of the white blood cell differential channel from 51 patients with APL, 510 scattergrams from 105 patients who had non-APL AML, and 320 scattergrams from 320 healthy controls were randomly stratified at a ratio of 4:1 and split into training and testing data sets to accomplish five-fold cross-validation. RESULTS: Both the area under the curve and the average precision of >0.99 were achieved in each fold. Three hundred four of the 320 APL scattergrams (95%) were correctly flagged by the model, which outcompeted the CBC review rules recommended by the International Society of Laboratory Hematology (all p < .001). External validation based on an independent testing data set that included 56 scattergrams from 31 patients with APL, 56 scattergrams from 55 patients with non-APL AML, and 64 scattergrams from 64 healthy controls also confirmed the sensitivity and specificity of the framework. CONCLUSIONS: To the authors' knowledge, their convolutional neural network-based framework is the first to use scattergram output from routine CBC analysis to map suspicious APL early with outstanding sensitivity, specificity, and precision. The authors also describe a new CBC workflow incorporating this framework upstream of the morphologic review, which would provide the earliest flag for APL. PLAIN LANGUAGE SUMMARY: The authors propose an innovative way to visualize complete blood counts (CBCs) by mapping the difference in white blood cell counts using automated CBC analysis to identify potential acute promyelocytic leukemia (APL) using a convolutional neural network (CNN), which can eliminate the potential pitfalls of manual observation. Analyses of an unprecedented, realistic data set validated that the quantitative relationship between the CBC scattergram and an APL abnormality is highly consistent. This is the first study to date focusing on screening for APL using scattergrams of the difference in white blood cell counts from routine CBC tests and has significant clinical relevance. The authors recommend using this method even before analyzing cell images, which could provide the earliest way to screen for APL in a sensitive and accurate way.

Adsorption of HF and H2S on α-Al2O3 (0001) Surfaces: A DFT Study.

Ex-service SF6 adsorbents in SF6 gas-insulated electric equipment contain many toxic substances. Inside, HF and H2S are two typical toxic gases. Based on the first principle, the interaction process between HF/H2S and α-Al2O3 (0001) surfaces was calculated using the density functional theory (DFT). The results showed that the adsorption of HF on α-Al2O3 (0001) is stronger than that of H2S. Under the five adsorption sites, the adsorption effect of HF-H and HF-F was similar. At O-2 site, the adsorption energy of H2S-H adsorption configuration is significantly higher than that of the other four sites. The density of states (DOS) indicated that new peaks appeared after adsorption. The DOS and partial density of states (PDOS) indicated that the adsorption of HF and H2S occurs via chemical adsorption. The DOS and PDOS shifted to the right when the S atom was approaching, proving that the system shifts to instability. Compared with the energy gap of α-Al2O3 (0001), HF and H2S adsorption systems decreased significantly. The energy gap of the HF adsorption system was 1.173 eV larger than that of the H2S system and the geometry was relatively stable, which is consistent with the DOS and PDOS adsorption calculation results. Thus, the adsorption of HF and H2S on α-Al2O3 (0001) surfaces was clearly different. The findings of this study may provide theoretical guidance for the adsorption of other gases or developing a new adsorbent.

Treatment and mortality of hemophagocytic lymphohistiocytosis in critically ill children: A systematic review and meta-analysis.

OBJECTIVE: Risk factors of mortality in critically ill children with hemophagocytic lymphohistiocytosis (HLH) are not well described. This systematic review aims to determine overall mortality of critically ill children with HLH, and describes etiologies, treatment, and pediatric intensive care unit (PICU) support employed. DATA SOURCES: PubMed, Embase, Web of Science, CINAHL, and Cochrane Library from inception until February 28, 2022. STUDY SELECTION: Observational studies and randomized controlled trials reporting children aged 18 years or below, diagnosed with HLH and admitted to the PICU. DATA EXTRACTION: Etiologies, treatment modalities, PICU therapies, and mortality outcomes were summarized. Random-effects meta-analysis was performed. DATA SYNTHESIS: Total 36 studies (total patients = 493, mean age: 49.5 months [95% confidence interval (CI): 30.9-79.5]) were included. Pooled mortality rate was 32.6% (95% CI: 23.4-42.4). The most frequent etiologies for HLH were infections (53.3%) and primary HLH (12.8%), while the remaining cases were due to other causes of secondary HLH, including autoimmune diseases, malignancy, and drug-induced and idiopathic HLH. Pooled mortality rate was higher in primary than secondary HLH (72.2%, 95% CI: 57.8-84.5 vs. 23.9%, 95% CI: 14.4-35.02; p < .01). Univariate analysis found that treatment with etoposide was associated with higher mortality, while intravenous immunoglobulins (IVIGs) were associated with lower mortality. Conversely, multivariable analysis adjusted for etiology demonstrated no association between etoposide and IVIG use, and mortality. Twenty-one studies (total patients = 278) had detailed information on PICU therapies. Mechanical ventilation (MV), continuous renal replacement therapy, and inotropes were used in 107 (38.5%), 66 (23.7%), and 51 patients (18.3%), respectively. Need for MV was associated with increased risk of mortality (mean difference = 28%, 95% CI: 9-47). CONCLUSION: Critically ill children with HLH have high mortality rates and require substantial PICU support. Collaborative work between multiple centers with standardized data collection can potentially provide more robust data.

Improved performance of UV-blue dual-band Bi2O3/TiO2 photodetectors and application of visible light communication with UV light encryption.

In this paper, self-powered photodetectors (PDs) with a dual-band photoresponse and excellent photodetection capabilities in complex environments can meet the needs of diverse detection targets, complex environments and diverse tasks. Herein, Bi2O3 nanosheets were deposited on the surface of TiO2 nanorod arrays (NRs) by chemical bath deposition (CBD) to construct self-powered heterojunction PDs with a UV-blue dual-band photoresponse. The nucleation and growth of Bi2O3 nanosheets on TiO2 NRs substrates were controlled by varying the concentration of the complexing agent triethanolamine (TEA) in the precursor solution, which regulated the morphology, crystalline quality and energy band structure as well as the photoelectronic properties of Bi2O3 films. The devices fabricated at a TEA concentration of 0.3 M exhibited excellent self-powered UV-blue dual-band photoresponse characteristics, achieving a photocurrent (Iph) of 144 nA, a responsivity of 1.79 mA W-1 and a detectivity of 5.94 × 1010 Jones under 405 nm illumination at 0 V, which can be attributed to the large built-in electric field (Eb) of Bi2O3/TiO2 heterojunctions, the low interfacial transfer resistance and suitable carrier transport path. In addition, Bi2O3/TiO2 heterojunction PDs with the UV-blue dual-band photoresponse characteristics can be applied in UV-encrypted visible light communication (VLC) with a light-controlled logic gate to improve the security of information transmission.

Signatures of necroptosis-related genes as diagnostic markers of endometriosis and their correlation with immune infiltration.

BACKGROUND: Endometriosis (EMS) occurs when normal uterine tissue grows outside the uterus and causes chronic pelvic pain and infertility. Endometriosis-associated infertility is thought to be caused by unknown mechanisms. In this study, using necroptosis-related genes, we developed and validated multigene joint signatures to diagnose EMS and explored their biological roles. METHODS: We downloaded two databases (GSE7305 and GSE1169) from the Gene Expression Omnibus (GEO) database and 630 necroptosis-related genes from the GeneCards and GSEA databases. The limma package in Rsoftware was used to identify differentially expressed genes (DEGs). We interleaved common differentially expressed genes (co-DEGs) and necroptosis-related genes (NRDEGs) in the endometriosis dataset. The DEGs functions were reflected by gene ontology analysis (GO), pathway enrichment analysis, and gene set enrichment analysis (GSEA). We used CIBERSORT to analyze the immune microenvironment differences between EMS patients and controls. Furthermore, a correlation was found between necroptosis-related differentially expressed genes and infiltrating immune cells to better understand the molecular immune mechanism. RESULTS: Compared with the control group, this study revealed that 10 NRDEGs were identified in EMS. There were two types of immune cell infiltration abundance (activated NK cells and M2 macrophages) in these two datasets, and the correlation between different groups of samples was statistically significant (P < 0.05). MYO6 consistently correlated with activated NK cells in the two datasets. HOOK1 consistently demonstrated a high correlation with M2 Macrophages in two datasets. The immunohistochemical result indicated that the protein levels of MYO6 and HOOK1 were increased in patients with endometriosis, further suggesting that MYO6 and HOOK1 can be used as potential biomarkers for endometriosis. CONCLUSIONS: We identified ten necroptosis-related genes in EMS and assessed their relationship with the immune microenvironment. MYO6 and HOOK1 may serve as novel biomarkers and treatment targets in the future.

Impact of total intravenous anesthesia and total inhalation anesthesia as the anesthesia maintenance approaches on blood glucose level and postoperative complications in patients with type 2 diabetes mellitus: a double-blind, randomized controlled trial.

BACKGROUND: Diabetes mellitus is a prevalent metabolic disease in the world. Previous studies have shown that anesthetics can affect perioperative blood glucose levels which related to adverse clinical outcomes. Few studies have explored the choice of general anesthetic protocol on perioperative glucose metabolism in diabetes patients. We aimed to compare total intravenous anesthesia (TIVA) with total inhalation anesthesia (TIHA) on blood glucose level and complications in type 2 diabetic patients undergoing general surgery. METHODS: In this double-blind controlled trial, 116 type 2 diabetic patients scheduled for general surgery were randomly assigned to either the TIVA group or TIHA group (n = 56 and n = 60, respectively). The blood glucose level at different time points were measured and analyzed by the repeated-measures analysis of variance. The serum insulin and cortisol levels were measured and analyzed with t-test. The incidence of complications was followed up and analyzed with chi-square test or Fisher's exact test as appropriate. The risk factors for complications were analyzed using the logistic stepwise regression. RESULTS: The blood glucose levels were higher in TIHA group than that in TIVA group at the time points of extubation, 1 and 2 h after the operation, 1 and 2 days after the operation, and were significantly higher at 1 day after the operation (10.4 ± 2.8 vs. 8.1 ± 2.1 mmol/L; P < 0.01). The postoperative insulin level was higher in TIVA group than that in TIHA group (8.9 ± 2.9 vs. 7.6 ± 2.4 IU/mL; P = 0.011). The postoperative cortisol level was higher in TIHA group than that in TIVA group (15.3 ± 4.8 vs. 12.2 ± 8.9 ug/dL ; P = 0.031). No significant difference regarding the incidence of complications between the two groups was found based on the current samples. Blood glucose level on postoperative day 1 was a risk factor for postoperative complications (OR: 1.779, 95%CI: 1.009 ~ 3.138). CONCLUSIONS: TIVA has less impact on perioperative blood glucose level and a better inhibition of cortisol release in type 2 diabetic patients compared to TIHA. A future large trial may be conducted to find the difference of complications between the two groups. TRIAL REGISTRATION: The protocol registered on the Chinese Clinical Trials Registry on 20/01/2020 (ChiCTR2000029247).

Biomechanical Effects of Prophylactic Knee Bracing on Anterior Cruciate Ligament Injury Risk: A Systematic Review.

OBJECTIVE: Prophylactic knee braces (PKBs) are widely used by athletes in pivoting and landing sports and have the potential to influence knee movement and alignment, thus modulating anterior cruciate ligament (ACL) injury risk. This systematic review analyses current evidence on the biomechanical effects that PKBs have in the prevention of ACL injuries. DATA SOURCES: The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searches were conducted on PubMed, Web of Science, Scopus, Ovid MEDLINE, EMBASE, Cochrane, and CINAHL for studies published from inception until May 31, 2021. Included studies assessed the effects of PKBs on biomechanical variables associated with ACL injuries in landing or pivoting tasks, comparing between braced and unbraced conditions. MAIN RESULTS: A total of 234 articles were identified; from which, 14 controlled, laboratory, biomechanical studies were included in this review. The effects of PKBs on knee biomechanics could be divided into kinematic variables in the coronal, sagittal, and transverse planes; and common kinetic variables, such as ground reaction force (GRF) and ACL load/strain. Also, PKBs were found to have protective effects in coronal and transverse plane kinematics, but results in the sagittal plane were inconclusive. Assessing knee kinetics, PKBs were advantageous in decreasing ACL load/strain but had no significant effect on GRF. CONCLUSIONS: Prophylactic knee braces may serve to reduce ACL injury risk by modulating knee coronal and transverse plane movements and ACL load/strain during high-risk maneuvres. Precise recommendations are limited by study heterogeneity. More prospective studies are needed to assess ACL injury risk during high-risk sports using specific PKBs.

Transplanted OECs Protect Visual Function by Regulating the Glutamate Metabolic Microenvironment in the Glaucoma Model.

BACKGROUND: Glaucoma is the leading cause of irreversible blindness, and the loss of retinal ganglion cells (RGCs) is the most important pathological feature. During the progression of glaucoma, glutamate content in the optic nerve increases, and glutamate-induced excitotoxicity will aggregate the damage and death of RGCs. We have previously reported that olfactory ensheathing cells (OECs) transplantation preserved the visual function of the glaucoma model but the mechanism is unknown. METHODS: Adult Long-Evans rats were used in the present study and injecting magnetic microspheres was used to establish a glaucoma model in rats. Optokinetic response test and Pattern electroretinogram recording were used to assess the visual functions of rats. RT-PCR, immunofluorescence, and co-culture experiments were performed to investigate the therapeutic effects and mechanisms of OECs for glaucoma. RESULTS: In the glaucoma model, increased glutamate content and the damage of astrocytes (AC) and RGCs were observed. OECs transplantation reduced the glutamate concentration in the optic nerve, alleviated the apoptosis of AC and RGCs, and protected the visual function of the glaucoma model. Furthermore, we found that OECs possessed a stronger capacity to metabolize excessive glutamate compared with AC and Müller glia. OECs could improve the glutamate microenvironment of the optic nerve to prevent AC and RGCs from glutamate-induced excitotoxicity in glaucoma. And the recovery of AC function further supported the survival of RGCs. CONCLUSIONS: We demonstrate that OECs transplantation could play a neuroprotective role by regulating the glutamate microenvironment in glaucoma.

Specific capture and determination of glycoprotein using a hybrid epitopes and monomers-mediated molecular-imprinted polymer enzyme-free electrochemical biosensor.

A novel molecular-imprinted polymer (MIP)-based enzyme-free biosensor was created for the selective detection of glycoprotein transferrin (Trf). For this purpose, MIP-based biosensor for Trf was prepared by electrochemical co-polymerization of novel hybrid monomers 3-aminophenylboronic acid (M-APBA) and pyrrole on a glassy carbon electrode (GCE) modified with carboxylated multi-walled carbon nanotubes (cMWCNTs). Hybrid epitopes of Trf (C-terminal fragment and glycan) have been selected as templates. The produced sensor exhibited great selective recognition ability toward Trf under optimal preparation conditions, offering good analytical range (0.125-1.25 µM) with a detection limit of 0.024 µM. The proposed hybrid epitope in combination with hybrid monomer-mediated imprinting strategy was successfully applied to detect Trf in spiked human serum samples, with recoveries and relative standard deviations ranging from 94.7 to 106.0% and 2.64 to 5.32%, respectively. This study provided a reliable protocol for preparing hybrid epitopes and monomers-mediated MIP for the synergistic and effective determination of glycoprotein in complicated biological samples.

Sponge-liked Silica Nanoporous Particles for Sustaining Release and Long-Term Antibacterial Activity of Natural Essential Oil.

To improve the sustained release and long-term antibacterial activity of Chimonanthus nitens Oliv. essential oil (CEO), novel sponge-liked nanoporous silica particles (SNP) were synthesized via the soft template method, which was employed as a biocompatible carrier to prepare spong-liked nanoporous silica particles loading with CEO (CEO-SNP) through physical adsorption. The structure and properties of the samples were characterized via N2 adsorption/desorption measurements, thermogravimetry (TGA), Fourier transform infrared, SEM and TEM. The result showed that the SNP exhibited an excellent loading capability of CEO up to 76.3%. The thermal stability and release behavior of the CEO were significantly improved via the physical adsorption of the SNP materials. The release profile of CEO was in accordance with the first-order kinetic model, which meant that the release mechanism was drug Fick's diffusion. The antibacterial evaluation results demonstrated that the CEO-SNP exhibited strong antibacterial activity against S. aureus, E. coli and P. aeruginosa. The antibacterial results have shown that the CEO-SNP could destroy the cell structure of bacteria, and result in the generation of oxidative stress and the release of nucleic acid. After storage of 30 d at 25 °C, the CEO-SNP still had the stronger antibacterial activity towards S. aureus, E. coli and P. aeruginosa in comparison with CEO. Therefore, the sponge-like silica nanoporous particles seemed to be a promising carrier for long-term stability and antibacterial delivery of CEO.

[Mechanism of Sijunzi Decoction in treatment of Alzheimer's disease based on UPLC-Q-TOF-MS, network pharmacology, and experimental verification].

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.

SCF/SCFR signaling plays an important role in the early morphogenesis and neurogenesis of human embryonic neural retina.

The stem cell factor receptor (SCFR) has been demonstrated to be expressed in the neural retina of mice, rat and human for decades. Previous reports indicated that the SCFR correlates with glia differentiation of late retinal progenitor cells (RPCs), retinal vasculogenesis and homeostasis of the blood-retinal barrier. However, the role of SCF/SCFR signaling in the growth and development of the neural retina (NR), especially in the early embryonic stage, remains poorly understood. Here, we show that SCF/SCFR signaling orchestrates invagination of the human embryonic stem cell (hESC)-derived NR via regulation of cell cycle progression, cytoskeleton dynamic and apical constriction of RPCs in the ciliary marginal zone (CMZ). Furthermore, activation of SCF/SCFR signaling promotes neurogenesis in the central-most NR via acceleration of the migration of immature ganglion cells and repressing apoptosis. Our study reveals an unreported role for SCF/SCFR signaling in controlling ciliary marginal cellular behaviors during early morphogenesis and neurogenesis of the human embryonic NR, providing a new potential therapeutic target for human congenital eye diseases such as anophthalmia, microphthalmia and congenital high myopia.

Intravenous infusion of small umbilical cord mesenchymal stem cells could enhance safety and delay retinal degeneration in RCS rats.

BACKGROUND: Human umbilical cord mesenchymal stem cells (UCMSCs) transplantation is a promising therapy for the treatment of retinitis pigmentosa (RP). However, intravenously infused cells may be blocked in the lung, increasing the risk of vascular obstruction, which needs to be optimized to further improve safety and efficacy. METHODS: We derived small UCMSCs (S-UCMSCs) from filtering UCMSCs with a 10-µm filter, and compared with UCMSCs by flow cytometry, directional differentiation culture and transcriptome sequencing. Then the S-UCMSCs and UCMSCs were intravenously infused in the Royal College Surgeons (RCS) rats to evaluate the safety and the efficacy. RESULTS: The diameter of S-UCMSCs ranged from 5.568 to 17.231 µm, with an average diameter of 8.636 ± 2.256 µm, which was significantly smaller than that of UCMSCs. Flow cytometry, immunofluorescence and transcriptome sequencing demonstrated that the S-UCMSCs and UCMSCs were the same kind of MSCs, and the S-UCMSCs were more proliferative. After the S-UCMSCs and UCMSCs were intravenously infused into the Royal College of Surgeons (RCS) rats at a dose of 1 × 106 cells/rat, the S-UCMSCs blocked in the lungs were significantly fewer and disappeared more quickly than UCMSCs. The b wave of the flash electroretinogram was improved at 7 d, and the retinal outer nuclear layer thickness was thicker at 7 d and 14 d. The expression level of inflammation was inhibited, and the expression level of neurotrophic factors was upregulated in the retina and serum after transplantation. CONCLUSIONS: S-UCMSCs intravenous infusion was safer than UCMSCs and could delay retinal degeneration and protect visual function in RCS rats, which may be a preferable therapeutic approach for RP.

Perioperative platelet count in peripheral blood is associated with the early stage of PND after major orthopedic surgery: a prospective observational study.

BACKGROUND: Perioperative neurocognitive disorders (PND) are common complications of major surgery among elderly patients, remarkably decreasing patients' life quality. Platelet count has been proved to be an essential factor in inflammation. However, as far as we know, the relationship between platelet count and PND is not clear yet in the orthopedic area. PND could be a long-term disease, which sometimes lasts for several years, and it is meaningful to find a biomarker of PND at the early stage. Thus, we designed this study to find out the association between perioperative platelet count and occurrence of PND, and determine whether preoperative platelet count could be a biomarker of the early stage of PND. METHODS: A prospective observational study was performed on the patients who would take total knee arthroplasty or total hip arthroplasty. Their peripheral platelets were counted by blood routine examination 1 day before and 3 days after the surgery. And we assessed their neurocognitive functions 1 day before and 3 days after the surgery. These data were recorded and analyzed to find out the relationship between platelet count and the occurrence of PND. RESULTS: Eventually, 70 patients finished the whole process, and 14 of them developed PND. The median preoperative platelet count in the PND group was significantly higher than that in the non-PND group (239 vs 168 × 10^9/L, p = 0.009). Preoperative platelet count was an independent risk factor for PND (odds ratio = 1.014, 95% confidence interval [CI] 1.000-1.027, P = 0.043) in the logistic multivariable regression, while the area under the curve of the receiver operating characteristic curve of the prediction model was 0.796 (95% CI 0.676-0.916). CONCLUSIONS: The higher preoperative and postoperative level of platelet count in the peripheral blood were associated with the early stage of PND, and preoperative platelet count could be a potential predictor of the early stage of PND in patients undergoing major orthopedic surgeries. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000033001 , registration date: 17 May 2020.

Interaction between 038R and 125R of Cherax quadricarinatus iridovirus (CQIV) and their effects on virus replication.

Iridovirids are a group icosahedral viruses containing linear double-stranded DNA, and mainly infect invertebrates and poikilothermic vertebrates. Cherax quadricarinatus iridovirus (CQIV) is a new species of the family Iridoviridae and can cause high mortality in shrimps. In CQIV genome, there are 25 conserved genes and the putative products are involved in several viral processes. In this study, three core protein including CQIV-032R, CQIV-125R and CQIV-160L were identified to interact with CQIV-038R by yeast two-hybrid (Y2H), and the interaction between CQIV-038R and CQIV-125R was further confirmed by co-immunoprecipitation (Co-IP) assays. In the expression system, EGFP-038R and mCherry-125R were colocalized in the cytoplasm when co-expressed in Sf9 cells. Moreover, silencing the expression of 038R, 125R or both of these two proteins respectively in C. quadricarinatus cells by small interfering RNAs showed significantly inhibit CQIV replication. Collectively, we identified the interaction between 038R and 125R, and demonstrated they are essential for CQIV replication.

Moderate Soil Drying-Induced Alternative Splicing Provides a Potential Novel Approach for the Regulation of Grain Filling in Rice Inferior Spikelets.

Poor grain filling of inferior spikelets, especially in some large-panicle rice varieties, is becoming a major limitation in breaking the ceiling of rice production. In our previous studies, we proved that post-anthesis moderate soil drying (MD) was an effective way to promote starch synthesis and inferior grain filling. As one of the most important regulatory processes in response to environmental cues and at different developmental stages, the function of alternative splicing (AS) has not yet been revealed in regulating grain filling under MD conditions. In this study, AS events at the most active grain-filling stage were identified in inferior spikelets under well-watered control (CK) and MD treatments. Of 16,089 AS events, 1840 AS events involving 1392 genes occurred differentially between the CK and MD treatments, many of which function on spliceosome, ncRNA metabolic process, starch, and sucrose metabolism, and other functions. Some of the splicing factors and starch synthesis-related genes, such as SR protein, hnRNP protein, OsAGPL2, OsAPS2, OsSSIVa, OsSSIVb, OsGBSSII, and OsISA1 showed differential AS changes under MD treatment. The expression of miR439f and miR444b was reduced due to an AS event which occurred in the intron where miRNAs were located in the MD-treated inferior spikelets. On the contrary, OsAGPL2, an AGPase encoding gene, was alternatively spliced, resulting in different transcripts with or without the miR393b binding site, suggesting a potential mechanism for miRNA-mediated gene regulation on grain filling of inferior spikelets in response to MD treatment. This study provides some new insights into the function of AS on the MD-promoted grain filling of inferior spikelets, and potential application in agriculture to increase rice yields by genetic approaches.