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The occurrence and development of inflammation are closely correlated to the polarization of macrophages. All-trans retinoic acid (ATRA) has been proven to promote the polarization of macrophages from M1 to M2, but this lacks an effective carrier to participate in the biological response. The present study aims to determine whether retinoic acid-incorporated glycol chitosan (RA-GC) nanoparticles can regulate macrophage polarization in Porphyromonas gingivalis-lipopolysaccharide (Pg-LPS)-induced inflammation.Mouse 264.7 cell lines were treated with 1 µg/mL Pg-LPS to induce inflammation. After the effects of ATRA and RA-GC on the activity of macrophages were detected by CCK-8 assay, cells induced with Pg-LPS were assigned to the blank control group (GC) nanoparticles without ATRA, and experimental groups (GC nanoparticles loaded with different concentrations of ATRA: 1, 10 and 100 µg/mL). The effects of RA-GC on inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-10 and IL-12 in macrophages were detected by enzyme-linked immunosorbent assay (ELISA). Subsequently, the effects of GC nanoparticles loaded with/without ATRA on macrophage polarization in an inflammatory environment were detected by RT-PCR and Western blotting.The results revealed that RA-GC had no significant effect on macrophage activity. However, RA-GC could effectively inhibit the Pg-LPS-induced inflammatory factor expression in macrophages. Meanwhile, the experimental results confirmed that RA-GC could downregulate the expression of inducible nitric oxide synthase (iNOS) (a marker of M1 macrophages) and upregulate the expression of mannose receptor and Arginase-1 (a marker of M2 macrophages) in a dose-dependent manner.The present study confirms that RA-GC can promote the M2 polarization of macrophages in an inflammatory environment, and proposes this as a promising target for the clinical treatment of Pg-LPS-related diseases.

Amyotrophic lateral sclerosis (ALS) is one of the most common fatal neurodegenerative diseases in adults. ALS pathogenesis is associated with toxic SOD1 aggregates generated by mutant SOD1. Since autophagy is responsible for the clearance of toxic protein aggregates including SOD1 aggregates, autophagy induction has been considered as a potential strategy for treating ALS. Autophagic signaling is initiated by unc-51 like autophagy activating kinase 1 (ULK1) complex. We previously identified that BL-918 as a specific ULK1 activator, which exerted cytoprotective effect against Parkinson's disease in vitro and in vivo. In this study we investigated whether BL-918 exerted a therapeutic effect against ALS, and characterized its pharmacokinetic profile in rats. In hSOD

Background Platelet parameters during pregnancy were associated with the risk of preeclampsia (PE), but the predictive value of these parameters for PE remained unclear. Our aim was to clarify the individual and incremental predictive value of platelet parameters, including platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) for PE. Methods This study was based on the Born in Guangzhou Cohort Study in China. Data on platelet parameters were extracted from medical records of routine prenatal examinations. Receiver operating characteristic (ROC) curve was performed to analyze the predictive ability of platelet parameters for PE. Maternal characteristic factors proposed by NICE and ACOG were used to develop the base model. Detection rate (DR), integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI) were calculated compared with the base model to assess the incremental predictive value of platelet parameters. Results A total of 30,401 pregnancies were included in this study, of which 376 (1.24%) were diagnosed with PE. Higher levels of PC and PCT were observed at 12–19 gestational weeks in women who developed PE later. However, no platelet parameters before 20 weeks of gestation reliably distinguished between PE complicated pregnancy and non-PE complicated pregnancy, with all values of the areas under the ROC curves (AUC) below 0.70. The addition of platelet parameters at 16–19 gestational weeks to the base model increased the DR for preterm PE from 22.9 to 31.4% at a fixed false positive rate of 5%, improved the AUC from 0.775 to 0.849 (p = 0.015), and yielded a NRI of 0.793 (p p = 0.035). Less but significant improvement in prediction performance was also observed for term PE and total PE when all the four platelet parameters were added to the base model. Conclusions Although no single platelet parameter at the early stage of pregnancy identified PE with high accuracy, the addition of platelet parameters to known independent risk factors could improve the prediction of PE.

Objective This study aims to assess the clinical efficacy and safety of omadacycline for the treatment of acute bacterial infections. Methods A search of PubMed, Embase, Cochrane Library, and Clinical Trials was conducted up to July 1, 2022. We included only randomized controlled trials (RCTs), in which omadacycline and other antibiotics were evaluated for treating acute bacterial infections in adults. The primary outcomes were clinical response and microbiological response, whereas the secondary outcome was the risk of adverse events (AEs). Results A total of seven RCTs involving 2841 patients with acute bacterial infection were included. Overall, our study illustrated that the clinical cure ratio of omadacycline was similar to the comparators in the treatment of acute bacterial infections (OR = 1.18, 95%CI = 0.96, 1.46, I2 = 29%). Omadacycline had a microbiological eradication rate similar to comparators in the treatment of acute bacterial infections (OR = 1.02, 95%CI = 0.81, 1.29, I2 = 42%). No statistical differences were observed between omadacycline and the comparators in terms of infection caused by Staphylococcus aureus (OR = 1.14, 95%CI = 0.80, 1.63, I2 = 0%), methicillin-resistant S. aureus (MRSA, OR = 1.28, 95%CI = 0.73, 2.24, I2 = 0%), methicillin-susceptible S. aureus (MSSA, OR = 1.12, 95%CI = 0.69, 1.81, I2 = 0%), and Enterococcus faecalis (OR = 2.47, 95%CI = 0.36, 16.97, I2 = 7%). A significant difference was found between omadacycline and the comparators for the risk of any AEs and treatment related AEs. The risk of discontinuation of the study drug due to an AEs was lower for omadacycline than for the comparators. Conclusion Omadacycline is as good as comparators in terms of efficacy and tolerance in the treatment of acute bacterial infections in adult patients. Thus, omadacycline is an appropriate option for antibiotic therapy in adult patients with acute bacterial infections.

Background Streptococcus dysgalactiae subsp. dysgalactiae has been identified as an animal pathogen that is thought to occur only in animal populations. Between 2009 and 2022, humans infected with SDSD were reported rarely. There is a lack of details on the natural history, clinical features, and management of disease caused by this pathogen. This case outlines a human SDSD with muscle aches and progressive loss of muscle strength leading to immobility and multi-organ dysfunction syndrome. Case presentation She presented with muscle pain and weakness, and later developed a sore throat, headache and fever with a maximum temperature of 40.5 °C. The muscle strength of the extremities gradually decreased to grade 1 and the patient was unable to move on his own. Next-generation blood sequencing and multi-culture confirmed the presence of Streptococcus dysgalactiae and Streptococcus dysgalactiae subsp. Dysgalactiae, respectively. A Sequential Organ Failure Assessment score of 6 indicated septicemia, and therapeutic antibiotics were prescribed empirically. After 19 days of inpatient treatment, the patient's condition greatly improved and completely recovered within a month. Conclusion Symptoms of Streptococcus dysgalactiae subsp. dysgalactiae presenting with progressive limb weakness resemble polymyositis, so a precise differential diagnosis is essential. Multidisciplinary consultation is helpful when polymyositis cannot be ruled out and facilitates the choice of an optimal treatment protocol. In the context of this case, penicillin is an effective antibiotic for Streptococcus dysgalactiae subsp. dysgalactiae infection.

Background Kallmann syndrome (KS) is a common type of idiopathic hypogonadotropic hypogonadism. To date, more than 30 genes including ANOS1 and FGFR1 have been identified in different genetic models of KS without affirmatory genotype–phenotype correlation, and novel mutations have been found. Methods A total of 35 unrelated patients with clinical features of disorder of sex development were recruited. Custom-panel sequencing or whole-exome sequencing was performed to detect the pathogenic mutations. Sanger sequencing was performed to verify single-nucleotide variants. Copy number variation-sequencing (CNV-seq) was performed to determine CNVs. The pathogenicity of the identified variant was predicted in silico. mRNA transcript analysis and minigene reporter assay were performed to test the effect of the mutation on splicing. Results ANOS1 gene c.709 T > A and c.711 G > T were evaluated as pathogenic by several commonly used software, and c.1063-2 A > T was verified by transcriptional splicing assay. The c.1063-2 A > T mutation activated a cryptic splice acceptor site downstream of the original splice acceptor site and resulted in an aberrant splicing of the 24-basepair at the 5′ end of exon 8, yielding a new transcript with c.1063–1086 deletion. FRFR1 gene c.1835delA was assessed as pathogenic according to the ACMG guideline. The CNV of del(8)(p12p11.22)chr8:g.36140000_38460000del was judged as pathogenic according to the ACMG & ClinGen technical standards. Conclusions Herein, we identified three novel ANOS1 mutations and two novel FGFR1 variations in Chinese KS families. In silico prediction and functional experiment evaluated the pathogenesis of ANOS1 mutations. FRFR1 c.1835delA mutation and del(8)(p12p11.22)chr8:g.36140000_38460000del were assessed as pathogenic variations. Therefore, our study expands the spectrum of mutations associated with KS and provides diagnostic evidence for patients who carry the same mutation in the future.

Background Systemic sclerosis (SSc; also known as “scleroderma”) is an autoimmune disorder characterized by extensive fibrosis, vascular changes, and immunologic dysregulation. Baicalein (phenolic flavonoid derived from Scutellaria baicalensis Georgi) has been used to treat the pathological processes of various fibrotic and inflammatory diseases. In this study, we investigated the effect of baicalein on the major pathologic characteristics of SSc: fibrosis, B-cell abnormalities, and inflammation. Methods The effect of baicalein on collagen accumulation and expression of fibrogenic markers in human dermal fibroblasts were analyzed. SSc mice were produced by injecting bleomycin and treated with baicalein (25, 50, or 100 mg/kg). The antifibrotic features of baicalein and its mechanisms were investigated by histologic examination, hydroxyproline assay, enzyme-linked immunosorbent assay, western blotting and flow cytometry. Results Baicalein (5–120 μM) significantly inhibited the accumulation of the extracellular matrix and fibroblast activation in transforming growth factor (TGF)-β1- and platelet derived growth factor (PDGF)-induced human dermal fibroblasts, as evidenced by abrogated deposition of total collagen, decreased secretion of soluble collagen, reduced collagen contraction capability and downregulation of various fibrogenesis molecules. In a bleomycin-induced model of dermal fibrosis in mice, baicalein (25–100 mg/kg) restored dermal architecture, ameliorated inflammatory infiltrates, and attenuated dermal thickness and collagen accumulation in a dose-dependent manner. According to flow cytometry, baicalein reduced the proportion of B cells (B220+ lymphocytes) and increased the proportion of memory B cells (B220+CD27+ lymphocytes) in the spleens of bleomycin-induced mice. Baicalein treatment potently attenuated serum levels of cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1 beta) and autoantibodies (anti-scleroderma 70 (Scl-70), anti-polymyositis-scleroderma (PM-Scl), anti-centromeres, anti-double stranded DNA (dsDNA). In addition, baicalein treatment can significantly inhibit the activation of TGF-β1 signaling in dermal fibroblasts and bleomycin-induce mice of SSc, evidenced by reducing the expression of TGF-β1 and IL-11, as well as inhibiting both small mother against decapentaplegic homolog 3 (SMAD3) and extracellular signal-related kinase (ERK) activation. Conclusions These findings suggest that baicalein has therapeutic potential against SSc, exerting modulating B-cell abnormalities, anti-inflammatory effects, and antifibrosis.

Photocatalytic reduction of U(VI) represents a novel and effective manner for the removal of U(VI) pollutant from radioactive wastewater. Herein, we successfully incorporated hydrogen into VO2 nanosheets, which strengthened the interaction between VO2 and U(VI), thereby achieving a highly active and stable photocatalyst for U(VI) reduction. With the increase of H content in hydric VO2 (HX-VO2) nanosheets, the bandgap shrank from 2.29 to 1.66 eV, whereas the position of conduction bands remained more negative than the reduction potential of U(VI)/U(IV) (0.41 V vs. NHE). When irradiated by simulated sunlight, the U(VI) removal efficiency over H0.613-VO2 nanosheets reached up to 95.4% within 90 min, which largely outperformed 28.3% of pristine VO2 nanosheets. The mechanistic study demonstrated that the hydroxylated surface gave rise to the balanced O confinement sites in VO2 (011), leading to the stabilized adsorption configuration and increased binding strength of UO22+ on HX−-VO2 nanosheets.

Background Citrullinemia type I (CTLN1) is a rare urea cycle disorder (UCD) with few adult cases described so far. Diagnosis of late-onset CTLN1 is difficult, and delayed treatment may increase the risk of severe hyperammonemia. Pregnancy is an important risk factor for women with CTLN1. However, the clinical manifestations of CTLN1 in a pregnant woman may be mistaken for pregnancy side effects and ultimately delay a timely diagnosis. Case presentation A 34-year-old woman developed vomiting and disturbance of consciousness after 12 weeks of gestation. A blood test showed hyperammonemia (454 μg/dL) with normal liver function tests. She fell into a deep coma, and her serum ammonia level increased to 800 μg/dL. Continuous renal replacement therapy (CRRT) was administered as a diagnostic treatment for UCD and serum ammonia. This patient’s case was complicated by co-infection; her dependents decided to withdraw life support and the patient died. She was diagnosed with CTLN1 by analyses of plasma amino acids, urinary orotic acid, and second-generation gene sequencing. Discussion and conclusion When a patient displays symptoms of emesis and disturbance of consciousness in early pregnancy, blood ammonia should be monitored, and UCD should be considered, particularly for patients with hyperammonemia in the absence of severe liver function abnormalities.

The characteristics of the waves around a lagoon entrance in South China Sea were observed during the past one and half years based on the wave measurements. The measured results show that the monsoon plays an important role. In summer, waves mostly come from the southeast, among which the wave components of non-dimensional periods larger than 0.2 are fetch-trapped waves. In winter the waves may be divided into two groups, the fetch-trapped waves and the waves from the open sea. The skewness of the directional distribution functions is within ±8 around zero. The power relationship between the direction spread and kurtosis is also investigated. Besides, it is found that the waves with the significant wave heights greater than 1.5 m are caused by typhoons or cold air. The frequency components of wave energy driven by cold air appear in the high frequency range at first, and change to the lower frequency range afterwards. The waves driven by typhoon mostly come from the open sea.

Background Laparoscopic-assisted repairs for pediatric inguinal hernia have gained gradual acceptance over the past decade. However, consensus about the optimal management is still lacking. The aim of this study is to compare outcomes of a modified laparoscope-assisted single-needle laparoscopic percutaneous extraperitoneal closure (LPEC) versus open repair of pediatric hernias/hydrocele in a single institution. Materials and methods We retrospectively reviewed the medical data of children who underwent laparoscope-assisted single-needle LPEC and open repair (OR) for inguinal hernia from 2014 to 2019. Data collection included demographics, laterality of hernia, surgical time and time to follow-up. We also reviewed and analyzed the evidence of recurrence, the incidence of metachronous contralateral inguinal hernia (MCIH), and other complications. Results In our cohort, 961 patients in the OR group and 1098 patients in the LPEC group were analyzed retrospectively. Mean operative time was significantly shorter in the LPEC group (22.3 ± 3.5 min) than in the OR group (27.8 ± 5.9 min) for bilateral hernia repair (p Conclusion Comparing to open technique, laparoscope-assisted single-needle LPEC provides a simple and effective option for pediatric inguinal hernia/hydrocele repair with excellent outcomes, a low incidence of recurrence, and reduced MCIH.

Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to various forms of cell death. It is believed that irreversible myocardial damage resulted from I/R occurs due to oxidative stress evoked during the reperfusion phase. Here we demonstrate that ischemia triggers a specific redox reaction of polyunsaturated fatty acids (PUFA)-phospholipids in myocardial cells, which acts as a priming signaling that initiates the outbreak of robust oxidative damage in the reperfusion phase. Using animal and in vitro models, the crucial lipid species in I/R injury were identified to be oxidized PUFAs enriched phosphatidylethanolamines. Using multi-omics, arachidonic acid 15-lipoxygenase-1 (ALOX15) was identified as the primary mediator of ischemia-provoked phospholipid peroxidation, which was further confirmed using chemogenetic approaches. Collectively, our results reveal that ALOX15 induction in the ischemia phase acts as a “burning point” to ignite phospholipid oxidization into ferroptotic signals. This finding characterizes a novel molecular mechanism for myocardial ischemia injury and offers a potential therapeutic target for early intervention of I/R injury.

Background Thyroid dysfunction has been reported in severe liver diseases. The aim of this study was to analyze the impact of serum thyroid-stimulation hormone (TSH) levels on the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). Methods This retrospective cohort study included 1,862 patients with HBV-related ACLF. Risk factors associated with 30-day and 90-day survival, hazard ratios (HRs), and 95% confidence intervals (CIs) for TSH were estimated using Cox proportional hazards regression. The Area Under the ROC curve (AUROC) analysis was carried out, and the cut-off values were calculated. After grouping by the cut-off value, survival was compared between the groups using the log-rank test. This study data is from the “Survival Cohort Study (SCS)”, which has been registered at ClinicalTrials.gov (NCT03992898). Results Multivariate analysis indicated that an elevated TSH level was a highly significant predictor for 30-day survival (HR = 0.743, 95% CI: 0.629–0.878, P P P P P P Conclusions Serum TSH level significantly correlate with HBV-related ACLF patients’ survival and may be of value for predicting 30-day and 90-day survival of patients with HBV-related ACLF.

This paper discusses the optimal control problems for a nonlinear age-structured two-species model, where elder individuals are more competitive than younger ones, and each species is described by a nonlinear integropartial differential equation with a global feedback boundary condition. First, we establish the existence of a unique nonnegative bounded solution by means of frozen coefficients and the fixed-point theorem. More importantly, we discuss the least deviation-cost problem and the most benefit-cost problem. For the least deviation-cost problem, the existence of an optimal strategy is established by means of Ekeland’s variational principle, and the minimum principle is obtained via an adjoint system. Meanwhile, the corresponding results for the most benefit-cost problem are given. In addition, some numerical experiment results are presented to examine the effects of parameters on the optimal policies and indexes.

We formulate a system of integro-differential equations to model the dynamics of competition in a two-species community, in which the mortality, fertility and growth are size-dependent. Existence and uniqueness of nonnegative solutions to the system are analyzed. The existence of the stationary size distributions is discussed, and the linear stability is investigated by means of the semigroup theory of operators and the characteristic equation technique. Some sufficient conditions for asymptotical stability / instability of steady states are obtained. The resulting conclusion extends some existing results involving age-independent and age-dependent population models.

During cancer therapy, phagocytic clearance of dead cells plays a vital role in immune homeostasis. The nonapoptotic form of cell death, ferroptosis, exhibits extraordinary potential in tumor treatment. However, the phagocytosis mechanism that regulates the engulfment of ferroptotic cells remains unclear. Here, we establish a novel pathway for phagocytic clearance of ferroptotic cells that is different from canonical mechanisms by using diverse ferroptosis models evoked by GPX4 dysfunction/deficiency. We identified the oxidized phospholipid, 1-steaoryl-2-15-HpETE-sn-glycero-3-phosphatidylethanolamine (SAPE-OOH), as a key eat-me signal on the ferroptotic cell surface. Enriching the plasma membrane with SAPE-OOH increased the efficiency of phagocytosis of ferroptotic cells by macrophage, a process that was suppressed by lipoprotein-associated phospholipase A2. Ligand fishing, lipid blotting, and cellular thermal shift assay screened and identified TLR2 as a membrane receptor that directly recognized SAPE-OOH, which was further confirmed by TLR2 inhibitors and gene silencing studies. A mouse mammary tumor model of ferroptosis verified SAPE-OOH and TLR2 as critical players in the clearance of ferroptotic cells in vivo. Taken together, this work demonstrates that SAPE-OOH on ferroptotic cell surface acts as an eat-me signal and navigates phagocytosis by targeting TLR2 on macrophages.

In this work, the graphene hydrogel (GH) was fabricated, and its adsorption behavior toward Th(IV) was studied. The GH displayed a porous network structure, with a controllable size and structure. The adsorption experimental results demonstrated that the adsorption of Th(IV) on GH fitted well with pseudo-second-order kinetic model and Freundlich isotherm model, with a maximum adsorption capacity of 190.28 mg/g at pH 3.0. The adsorption of Th(IV) on GH in inner-sphere surface complexation. Solution pH has an important influence on Th(IV) adsorption of GH. In addition, the GH exhibits an excellent reusability in Th(IV) adsorption.

GM1 ganglioside is particularly abundant in the mammalian central nervous system and has shown beneficial effects on neurodegenerative diseases. In this study, we investigated the therapeutic effect of GM1 ganglioside in experimental models of Parkinson’s disease (PD) in vivo and in vitro. Mice were injected with MPTP (30 mg·kg(-1)·d(−1), i.p.) for 5 days, resulting in a subacute model of PD. PD mice were treated with GM1 ganglioside (25, 50 mg·kg(−)(1)·d(−1), i.p.) for 2 weeks. We showed that GM1 ganglioside administration substantially improved the MPTP-induced behavioral disturbance and increased the levels of dopamine and its metabolites in the striatal tissues. In the MPP(+)-treated SH-SY5Y cells and α-synuclein (α-Syn) A53T-overexpressing PC12 (PC12(α-Syn A53T)) cells, treatment with GM1 ganglioside (40 μM) significantly decreased α-Syn accumulation and alleviated mitochondrial dysfunction and oxidative stress. We further revealed that treatment with GM1 ganglioside promoted autophagy, evidenced by the autophagosomes that appeared in the substantia nigra of PD mice as well as the changes of autophagy-related proteins (LC3-II and p62) in the MPP(+)-treated SH-SY5Y cells. Cotreatment with the autophagy inhibitor 3-MA or bafilomycin A1 abrogated the in vivo and in vitro neuroprotective effects of GM1 ganglioside. Using GM1 ganglioside labeled with FITC fluorescent, we observed apparent colocalization of GM1-FITC and α-Syn as well as GM1-FITC and LC3 in PC12(α-Syn A53T) cells. GM1 ganglioside significantly increased the phosphorylation of autophagy regulatory proteins ATG13 and ULK1 in doxycycline-treated PC12(α-Syn A53T) cells and the MPP(+)-treated SH-SY5Y cells, which was inhibited by 3-MA. Taken together, this study demonstrates that the anti-PD role of GM1 ganglioside resulted from activation of autophagy-dependent α-Syn clearance.

We study the dynamics of snakelike similaritons to the nonlinear Schrodinger equation in combined harmonic-lattice potentials with a varying source term. Using the self-similar and Mobius transformations, we construct a large number of analytical solutions which generate many types of novel snakelike similaritons under some constraint conditions, such as the W- and bell-shaped breathing similaritons and the elliptic function solutions. Then, four specific examples of physical interest are considered in details to show the dynamical behaviors of the similaritons. Especially, the compression effect of snakelike similaritons is demonstrated in dispersion-decreasing media with Bessel modulated nonlinearity. We find that the structures of snakelike similaritons can be controlled by tuning the coefficient parameters, the combined harmonic-lattice potentials, and the source term. The stability of the solutions has also been performed by numerical simulations. Our results may have potential applications in the dual-core fiber waveguides and Bose–Einstein condensates in the presence of an inhomogeneous source.

Excessive nitric oxide (NO) causes extensive damage to the nervous system, and the adrenergic system is disordered in many neuropsychiatric diseases. However, the role of the adrenergic system in protection of the nervous system against sodium nitroprusside (SNP) injury remains unclear. In this study, we investigated the effect of ganoderic acid A (GA A) against SNP injury in neural cells and the role of adrenergic receptors in GA A neuroprotection. We found that SNP (0.125−2 mM) dose-dependently decreased the viability of both SH-SY5Y and PC12 cells and markedly increased NO contents. Pretreatment with GA A (10 μM) significantly attenuated SNP-induced cytotoxicity and NO increase in SH-SY5Y cells, but not in PC12 cells. Furthermore, pretreatment with GA A caused significantly higher adrenaline content in SH-SY5Y cells than in PC12 cells. In order to elucidate the mechanism of GA A-protecting SH-SY5Y cells, we added adrenaline, phentolamine, metoprolol, or ICI 118551 1 h before GA A was added to the culture medium. We found that addition of adrenaline (10 μM) significantly improved GA A protection in PC12 cells. The addition of β1-adrenergic receptor antagonist metoprolol (10 μM) or β2-adrenergic receptor antagonist ICI 118551 (0.1 μM) blocked the protective effect of GA A, whereas the addition of α-adrenergic receptor antagonist phentolamine (0.1 μM) did not affect GA A protection in SH-SY5Y cells. These results suggest that β-adrenergic receptors play an important role in the protection of GA A in SH-SY5Y cells against SNP injuries, and excessive adrenaline system activation caused great damage to the nervous system.

Clinical trials and treatment guidelines for myelodysplastic syndrome depend on several prognostic scoring systems to stratify patients by risk. These include different variables: the degree of cytopenia, percentage of bone marrow blasts, and cytogenetics. Little is known about the impact of bone marrow blasts in patients with adverse cytogenetics. In this retrospective study, we analyzed 536 patients with high-grade myelodysplastic syndrome to examine the differences in survival for patients with different percentages of bone marrow blasts. The median overall survival in patients with ≥ 5% marrow blasts was not statistically different from that for patients with

This study evaluates newly diagnosed IgM (6%, n = 75/1174) vs. non-IgM light chain amyloidosis patients. IgM amyloid patients had lower light chains (12.5 vs. 22.5 mg/dL; p 1 organ involvement (31% vs. 44%, p = 0.02) was less common in IgM amyloidosis, while soft tissue and peripheral nerve involvement was more common. t(11;14) was less common (27% vs. 50%, p = 0.008) in IgM amyloidosis. Rates of MYD88L265P and CXCR4WHIM mutation in IgM amyloidosis were 58% (29/50) and 17% (8/46). Diagnosis after hematopathology review in IgM amyloidosis was pure plasma cell neoplasm (PPCN) in 23% (16/70), lymphoplasmacytic neoplasm (LPL) in 63% (44/70) patients, and other (14%). LPL vs. PPCN groups had distinct genetic abnormalities: t(11;14): 0% (0/18) vs. 60% (9/15), p

Transducin-like enhancer of Split3 (TLE3) serves as a transcriptional corepressor during cell differentiation and shows multiple roles in different kinds of cancers. Recently, TLE3 together with many other genes involved in Wnt/β-catenin pathway were detected hyper-methylated in colorectal cancer (CRC). However, the potential role and the underlying mechanism of TLE3 in CRC progression remain scarce. Gene expression profiles were analyzed in The Cancer Genome Atlas (TCGA) microarray dataset of 41 normal colorectal intestine tissues and 465 CRC tissues. Western blot and Real-time Quantitative PCR (RT-qPCR) were respectively performed to detect protein and mRNA expression in 8 pairs of CRC tissue and matched adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to evaluate TLE3 protein expression in 105 paraffin-embedded, archived human CRC tissues from patients, whose survival data were analyzed with Kaplan-Meier method. In vitro experiments including MTT assay, colony formation assay, and soft agar formation assay were used to investigate the effects of TLE3 on CRC cell growth and proliferation. Additionally, subcutaneous tumorigenesis assay was performed in nude mice to confirm the effects of TLE3 in vivo. Furthermore, gene set enrichment analysis (GSEA) was run to explore potential mechanism of TLE3 in CRC, and then we measured the distribution of CRC cell cycle phases and apoptosis by flow cytometry, as well as the impacts of TLE3 on MAPK and AKT signaling pathways by Western blot and RT-qPCR. TLE3 was significantly down-regulated in 465 CRC tissues compared with 41 normal tissues. Both protein and mRNA expressions of TLE3 were down-regulated in CRC compared with matched adjacent normal mucosa. Lower expression of TLE3 was significantly associated with poorer survival of patients with CRC. Besides, knock down of TLE3 promoted CRC cell growth and proliferation, while overexpression of TLE3 showed suppressive effects. Furthermore, overexpression of TLE3 caused G1-S phase transition arrest, inhibition of MAPK and AKT pathways, and up-regulation of p21Cip1/WAF1 and p27Kip1. This study indicated that TLE3 repressed CRC proliferation partly through inhibition of MAPK and AKT signaling pathways, suggesting the possibility of TLE3 as a biomarker for CRC prognosis.

Birth weight is a strong determinant of infant short- and long-term health outcomes. Family socioeconomic position (SEP) is usually positively associated with birth weight. Whether this association extends to abnormal birth weight or there exists potential mediator is unclear. We analyzed data from 14,984 mother-infant dyads from the Born in Guangzhou Cohort Study. We used multivariable logistic regression to assess the associations of a composite family SEP score quartile with macrosomia and low birth weight (LBW), and examined the potential mediation effect of maternal pre-pregnancy body mass index (BMI) using causal mediation analysis. The prevalence of macrosomia and LBW was 2.62% (n = 392) and 4.26% (n = 638). Higher family SEP was associated with a higher risk of macrosomia (OR 1.30, 95% CI 0.93–1.82; OR 1.53, 95% CI 1.11–2.11; and OR 1.59, 95% CI 1.15–2.20 for the 2nd, 3rd, and 4th SEP quartile respectively) and a lower risk of LBW (OR 0.69, 95% CI 0.55–0.86; OR 0.76, 95% CI 0.61–0.94; and OR 0.61, 95% CI 0.48–0.77 for the 2nd, 3rd, and 4th SEP quartile respectively), compared to the 1st SEP quartile. We found that pre-pregnancy BMI did not mediate the associations of SEP with macrosomia and LBW. Socioeconomic disparities in fetal macrosomia and LBW exist in Southern China. Whether the results can be applied to other populations should be further investigated.

We present a series of snakelike self-similar solutions to the nonlinear Schrodinger equation with a gain in the presence of an external source through asymmetric dual-core waveguide amplifiers with a long-period grating. The asymmetric dual-core waveguide is composed of two adjoining, closely spaced, upper and lower waveguides, in which the upper one is an active graded-index waveguide with a long-period grating along the medium, while the lower one is a passive step-index waveguide. The results show that: (1) the self-similar optical structures can be generated and effectively controlled by modulating the amplitude of the source; (2) the long-period grating can change the motion of the solutions and preserve their shapes. These results may raise the possibility of some experiments and potential applications in the graded-index grating waveguide amplifier with an external source.

We examine to what extent the l1 norm of coherence through an open quantum system is affected by noise. To discuss the effect of the noise, we give a definition of the decay rate of the l1 norm of coherence, i.e., the value of the coherence of initial states divided by the coherence of final states. Then we use the measure of the decay of coherence to discuss to what extent several noisy channels affects the coherence. We find that the decay rate is independent of the initial state parameters but only related to parameters of the phase flip channels, the depolarizing channels, and the amplitude channels. However, the decay rate is related to the initial state parameters and parameters of the bit flip channels. Contrary to the view at first glance, we find that the bit flip channels even have cohering power.

Background Prevalence of neonatal microcephaly in populations without Zika-epidemics is sparse. The study aimed to report baseline prevalence of congenital microcephaly and its relationship with prenatal factors in an area at risk of Zika outbreak. Methods This study included singletons born after 24 gestational weeks in 2017–2018 at four hospitals in Guangzhou, China. Microcephaly was defined as a head circumference at birth >3SD below the mean for sex and gestational age. Prevalence of microcephaly was estimated by binomial exact method. Multivariable logistic regression was used to examine the associations of microcephaly with prenatal factors. The population attributable fraction (PAF) for associated risk factors was calculated. Results Of 46,610 live births included, 154 (3.3, 95% CI 2.8–3.9 per 1000 live births) microcephalies were identified. Maternal hepatitis B virus carriers (HBV, OR 1.80, 95% CI 1.05–3.10) and primipara (OR 2.68, 95% CI 1.89–3.81) had higher risk of having a microcephalic baby. Higher prevalence of microcephaly was observed in women who had premature labor (OR 1.98, 95% CI 1.17–3.34) and had a baby with fetal growth restriction (OR 16.38, 95% CI 11.81–22.71). Four identified factors (HBV, primiparity, preterm labor, and fetal growth restriction) contributed to 66.4% of the risk of microcephaly. Conclusions The prevalence of microcephaly in Guangzhou was higher than expected. This study identified four prenatal risk factors that, together, contributed to two-thirds of the increased risk of microcephaly. This is the first reported association between maternal HBV carrier status and microcephaly.

Global Navigation Satellite System (GNSS) coordinate time series contains significant information on plate movement and crustal deformation. Through using GAMIT/GLOBK software, we obtained the coordinate time series of Anhui Continuously Operating Reference System (AHCORS) from 2013 to 2018.5. Then power spectral density method and the maximum likelihood estimation method were applied to determine the optimal noise model of AHCORS for the first time. Our results show that the White Noise plus Flicker Noise (WN+FN) model represents the best model for this region. We then solved the linear trend of the obtained coordinate time series using CATS software. Overall, the velocity uncertainty with colored noise is 7 ~ 10 times of that with white noise only, while the average horizontal velocity based on the Eurasian plate is 6.43 mm/a during this period, with a direction of E29.10°S. With respect to the vertical velocity, there is a tendency of subsidence in the north and uplift in the south, with maximum subsidence reaching up to 32.82 mm/a, which appears at station SZDS in Dangshan, Suzhou. The rapid subsidence at this area is most likely due to extraction of groundwater and mineral resources in recent years.

Although stress has been known to increase the susceptibility of pathogen infection, the underlying mechanism remains elusive. In this study, we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus (H1N1) and obviously aggravated lung inflammation. Corticosterone (CORT), a main type of glucocorticoids in rodents, was secreted in the plasma of stressed mice. We further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling (MAVS) protein-transduced IFN-β production without affecting its mRNA level, while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in mice. Mechanistically, the effect of CORT was mediated by proteasome-dependent degradation of MAVS, thereby resulting in the impediment of MAVS-transduced IFN-β generation in vivo and in vitro. Furthermore, RNA-seq assay results indicated the involvement of Mitofusin 2 (Mfn2) in this process. Gain- and loss-of-function experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of MAVS. Co-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2 (HR1), MAVS (C-terminal/TM) and SYVN1 (TM). Collectively, our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a ‘fine tuning’ of antiviral innate immunity in response to influenza infection under stress.

The increasing number of applications of nanoparticles (NPs) in various fields has led to negative effects on the environment. In this study, the effects of CuO nanoparticles (CuO NPs) on Arabidopsis root tips were investigated. Significant growth inhibition on Arabidopsis roots was observed after treatment with both CuO NPs (10 mg/L) and the correspondingly released Cu2+ (0.80 mg/L). Scanning electron microscope images demonstrated that NPs primarily deposited on the surface of root tips and penetrated intercellular spaces after CuO NP exposure. Light and fluorescence microscope visualization revealed that the root tips were damaged severely after CuO NP exposure, with swelling of the hair zone, splitting of the cell wall junction, and disordered cell arrangement in the root tip. Semiquantitative analysis by Fourier transform infrared spectroscopy demonstrated that the cell wall xyloglucan and esterified pectin contents in the roots were decreased. Similar but weaker effects on the roots were detected after Cu2+ treatment. Additionally, some genes related to cell wall organization were downregulated by CuO NP stress, partially contributing to the cell wall component change. The results demonstrated that CuO NPs produced phytotoxicity to the cell wall through both physical damage and biochemical disruption, causing loosening of the tethers between cellulose microfibrils in the cell wall and the disruption of cell adhesion. The phytotoxicity of CuO NPs in the plant cell wall was mainly caused by NPs and was partially related to the released Cu2+. These findings are helpful to understand better the negative effects of CuO NPs on plant regarding the cell wall.

Caffeine is a major component of xanthine alkaloids and commonly consumed in many popular beverages. Due to its occasional side effects, reduction of caffeine in a natural way is of great importance and economic significance. Recent studies reveal that caffeine can be converted into non-stimulatory theacrine in the rare tea plant Camellia assamica var. kucha (Kucha), which involves oxidation at the C8 and methylation at the N9 positions of caffeine. However, the underlying molecular mechanism remains unclear. Here, we identify the theacrine synthase CkTcS from Kucha, which possesses novel N9-methyltransferase activity using 1,3,7-trimethyluric acid but not caffeine as a substrate, confirming that C8 oxidation takes place prior to N9-methylation. The crystal structure of the CkTcS complex reveals the key residues that are required for the N9-methylation, providing insights into how caffeine N-methyltransferases in tea plants have evolved to catalyze regioselective N-methylation through fine tuning of their active sites. These results may guide the future development of decaffeinated drinks., Kucha is a rare variety of tea tree that produces the non-stimulatory theacrine instead of caffeine. Here the authors show that theacrine synthase from Kucha has N9-methyltransferase activity resulting from amino acid substitutions that explain substrate specificity and could potentially guide production of caffeine-free tea.

Patients with a sole del(20q) chromosomal abnormality and without morphologic features of a myeloid neoplasm (MN) have shown variable clinical outcomes. To explore the potential risk stratification markers in this group of patients, we evaluated their genetic mutational landscape by a 35-gene MN-focused next-generation sequencing (NGS) panel and examined the association of mutations to progression of MNs. Our study included 56 patients over a 10-year period with isolated del(20q), of whom 23 (41.1%) harbored at least one mutation. With a median follow-up of 32.6 months (range: 0.1−159.1), 9 of 23 patients with mutation(s) progressed to MNs, while all 33 patients without mutations did not progress to MN. Kaplan−Meier survival analysis demonstrated the presence of mutation(s) as a significant risk factor for progression to MN (P < 0.0001). MN progression was strongly associated with the presence of non-DNMT3A/TET2/ASXL1 epigenetic modifiers and nonspliceosome mutations (P = 0.003). There was no significant difference among patients with and without MN progression with respect to the number of mutations, variant allele frequency, percentage of del(20q), and other clinical/laboratory variables. This study illustrates the underlying genetic heterogeneity and complexity of isolated del(20q), and underscores the prognostic value of NGS mutational analysis in these cases.

A new method for structural damage identification is presented based on perturbations of curvature mode shape and frequency. Firstly, the structure’s mass and stiffness matrices are expressed as functions of its elements’ physical parameters, which reflect their damage states. According to differences in the curvature mode shape of the structure in undamaged and damaged states, possible damage equations and determined damage equations are established and used to solve for the elements’ damage parameters. Then, to ensure the accuracy of the recognition result, a reasonable solution is substituted into a damage-checking equation based on the change of frequency of the damaged structure. Numerical examples are used to show that, to identify the damage, only one order mode needs to be tested. When the degree of damage is low, first-order perturbation equations can be used to recognize the damage with sufficient accuracy. If the extent of the damage is high, second-order perturbation equations can be used to provide more accurate identification results.