Assembly of Functional Co(II) Metal-Organic Frameworks through a Mixed Ligand Strategy: Structure and Photocatalytic Degradation Properties.

Four Co(II)-based metal-organic frameworks (MOFs) were constructed by a mixed ligand strategy under solvothermal conditions. The controllable modification of the bridging groups in the secondary building units was realized by changing the anions in MOFs 1-3. The MOF 4 with 3D framework structure was obtained by regulating the solvent ratio following the synthesis process of MOF 3. Furthermore, the MOFs 1-4 exhibited efficient photocatalytic activity for the degradation of malachite green (MG) dye without any photosensitizer or cocatalyst under a low-energy light source, the decolorization ratio of MG all reached more than 96.0% within 60 min, and maximal degradation was obtained to be 99.4% (MOF 4). The recycling experiments showed that the degradation rate of MG was still higher than 91% after 10 cycles. In the MOF 4 as representation, the photocatalytic process was explored systematically. The possible mechanism of catalytic degradation was discussed, which proved the existence of efficient oxidation active factors (•O2-, •OH, and h+). The possible intermediates and degradation pathways were investigated based on high-performance liquid chromatography tandem mass spectrometry. Additionally, MOFs 1-4 also exhibited excellent photocatalytic activity for the degradation of methylene blue, methyl violet, rhodamine B, and basic red 9.

Appropriate induction of TOC1 ensures optimal MYB44 expression in ABA signaling and stress response in Arabidopsis.

Plants possess the remarkable ability to integrate the circadian clock with various signalling pathways, enabling them to quickly detect and react to both external and internal stress signals. However, the interplay between the circadian clock and biological processes in orchestrating responses to environmental stresses remains poorly understood. TOC1, a core component of the plant circadian clock, plays a vital role in maintaining circadian rhythmicity and participating in plant defences. Here, our study reveals a direct interaction between TOC1 and the promoter region of MYB44, a key gene involved in plant defence. TOC1 rhythmically represses MYB44 expression, thereby ensuring elevated MYB44 expression at dawn to help the plant in coping with lowest temperatures during diurnal cycles. Additionally, both TOC1 and MYB44 can be induced by cold stress in an Abscisic acid (ABA)-dependent and independent manner. TOC1 demonstrates a rapid induction in response to lower temperatures compared to ABA treatment, suggesting timely flexible regulation of TOC1-MYB44 regulatory module by the circadian clock in ensuring a proper response to diverse stresses and maintaining a balance between normal physiological processes and energy-consuming stress responses. Our study elucidates the role of TOC1 in effectively modulating expression of MYB44, providing insights into the regulatory network connecting the circadian clock, ABA signalling, and stress-responsive genes.

Bibenzyl and naphthalene derivatives from Dendrobium chrysanthum and their anti-hepatic-steatosis activities.

In this study, 16 new compounds, six bibenzyls (1-6) and 10 naphthalenes (7-13), including three pairs of naphthalene enantiomers and three known compounds (14-16), were isolated from Dendrobium chrysanthum. Structurally, compounds 1-5 are previously undescribed dimeric bibenzyls, uniquely linked by unusual carbon bonds. The structures of the compounds were determined using spectroscopy and X-ray crystallography. The screening results indicated that 1, 2, and 5 showed remarkable lipid-lowering activities in FFA-induced HepG2 cells, with EC50 values ranging from 3.13 to 6.57 µM. Moreover, 1, 2, and 5 significantly decreased both the mRNA and protein levels of the target SREBP-1c, and 5 also reduced PPARα mRNA and protein levels. Therefore, 1, 2, and 5 are potential drugs against hepatic steatosis by targeting PPARα or SREBP-1c.

Alleviation of allergic asthma by rosmarinic acid via gut-lung axis.

BACKGROUND: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. PURPOSE: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. METHODS: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. RESULTS: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. CONCLUSIONS: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.

Impact of hemoglobin adducts of ethylene oxide on the prevalence and prognosis of chronic kidney disease in US adults: an analysis from NHANES 2013-2016.

Animal experiments have shown that high exposure to ethylene oxide (EO) can cause multiple system damages including the renal system. Recent studies have reported associations between exposure to EO and cancer, dyslipidemia, diabetes, and cardiovascular disease. However, the impact of exposure to EO on the prevalence and prognosis of chronic kidney disease (CKD) in humans is scarcely investigated. The study was designed to investigate the associations between EO exposure and incidence and prognosis of CKD among 2900 US adults. Exposure to EO was measured by detecting the levels of hemoglobin adducts of EO (HbEO). The diagnosis of CKD was made according to an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) > 30 mg/g. Prognosis of CKD was assessed based on the evaluation system initiated by KDIGO that consists of eGFR and UACR. Survey-weighted generalized linear models and proportional odds models were constructed to assess the associations between HbEO and prevalence and prognosis of CKD, with odds ratios (ORs) and proportional odds ratios (PORs) and their 95% confidence intervals (CIs) reported, respectively. Restricted cubic spline (RCS) function was performed to depict the correlation between HbEO and CKD. The weighted median (interquartile range) of HbEO was 31.3 (23.1-60.3) pmol/g Hb. A total of 491 participants (16.9%) were diagnosed with CKD, and 153 participants (5.31%) were identified to be at high or very high risk. Referred to the first tertile of HbEO, the adjusted ORs (95% CIs) for CKD in the second and third tertile were 1.46 (0.85, 2.50) and 1.69 (1.00, 2.85), and the adjusted PORs (95% CIs) for prognosis of CKD in the second and third tertile were 1.37 (0.94, 1.99) and 1.58 (1.10, 2.26). When HbEO was analyzed as a continuous variable, the adjusted OR (95% CI) for CKD and POR (95% CI for prognosis of CKD were 1.24 (0.97, 1.58) and 1.22 (1.01, 1.47), respectively. RCS analysis revealed a non-linear positive correlation between HbEO and prevalence of CKD (P for nonlinearity < 0.05). Subgroup analysis indicated smoking status had a significant impact on this association, which remained significant among never smokers but lost significance among smokers. Among US adults, increased EO exposure was independently related to increased CKD prevalence and poor CKD outcomes, which was established in never smokers but not among ever smokers.

[Blinatumomab as bridging therapy in two children with B-cell acute lymphoblastic leukemia complicated by invasive fungal disease]. / 2例急性Bæ·‹å·´ç»†èƒžç™½è¡€ç— åˆå¹¶ä¾µè¢­æ€§çœŸèŒç— å„¿ç«¥åº”ç”¨è´æž—å¦¥æ¬§å•æŠ—æ¡¥æŽ¥æ²»ç–—åˆ†æž.

This article reports two cases of children with B-cell acute lymphoblastic leukemia (B-ALL) complicated by invasive fungal disease (IFD) who received bridging treatment using blinatumomab. Case 1 was a 4-month-old female infant who experienced recurrent high fever and limb weakness during chemotherapy. Blood culture was negative, and next-generation sequencing (NGS) of peripheral blood, bronchoalveolar lavage fluid, and cerebrospinal fluid were all negative. Chest CT and cranial MRI revealed obvious infection foci. Case 2 was a 2-year-old male patient who experienced recurrent high fever with multiple inflammatory masses during chemotherapy. Candida tropicalis was detected in peripheral blood and abscess fluid using NGS, while blood culture and imaging examinations showed no obvious abnormalities. After antifungal and blinatumomab therapy, both cases showed significant improvement in symptoms, signs, and imaging, and B-ALL remained in continuous remission. The report indicates that bridging treatment with blinatumomab in children with B-ALL complicated by IFD can rebuild the immune system and control the underlying disease in the presence of immunosuppression and severe fungal infection.

A distribution-based selective optimization method for eliminating periodic defects in harmonic signals.

Due to environmental interference and defects in measured objects, measurement signals are frequently affected by unpredictable noise and periodic defects. Moreover, there is a lack of effective methods for accurately distinguishing defect components from measurement signals. In this study, a distribution-based selective optimisation method (SOM) is proposed to mitigate the effects of noise and defect components. The SOM can be seen as a binary- or multiple-class signal classifier based on an error distribution, which can simultaneously eliminate periodic defect components of measurement signals and proceed with signal-fitting regression. The effectiveness, accuracy, and feasibility of the SOM are verified in theoretical and realworld measurement settings. Based on theoretical simulations under various parameter conditions, some criteria for selecting operation variables among a selection of parameter conditions are explained in detail. The proposed method is capable of separating defect components from measurement signals while also achieving a satisfactory fitting curve for the measurement signals. The proposed SOM has broad application prospects in signal processing and defect detection for mechanical measurements, electronic filtering, instrumentation, part maintenance, and other fields.

Stable Co(II)-based coordination polymer as fluorescence sensor for the discriminative sensing of biomarker methylmalonic acid.

Three novel Co-based coordination polymers including {[Co(L)(µ3-O)1/3]2}n (1), {[Co(L)(bimb)]}n (2) and {[Co(L)(bimmb)1/2]}n (3) (H2L = 2,6-di(4-carboxylphenyl)-4-(4-(triazol-1-ylphenyl))pyridine), bimb = 1,4-bis(lmidazol) butane, bimmb = 1,4-bis(imidazole-1-ylmethyl)benzene) were successfully prepared under solvothermal conditions and characterized. Single-crystal X-ray diffraction analyses revealed that 1 possesses a 3D architecture composed of a trinuclear cluster [Co3N3(CO2)6(µ3-O)], 2 exhibits a 2D new topological framework with the point symbol (84·122)(8)2, whereas 3 shows a unique six-fold interpenetrated 3D framework with a (63·82·10)2(63)2(8) topology. Impressively, all of them can function as a highly selective and sensitive fluorescent sensor for the biomarker methylmalonic acid (MMA) via fluorescence quenching. The low detection limit, reusability and high anti-interference performance together make 1-3 become promising sensors for the practical detection of MMA. Furthermore, the successful application of MMA detection in urine sample was demonstrated, which may be a potential candidate for the further development of clinical diagnostic tools.

Berberine stimulates lysosomal AMPK independent of PEN2 and maintains cellular AMPK activity through inhibiting the dephosphorylation regulator UHRF1.

Aim: AMPK is the key regulatory kinase mediating the effect of berberine (BBR) and metformin on metabolic improvement. The present study investigated the mechanism of BBR on AMPK activation at low doses, which was different from that of metformin. Methods: Lysosomes were isolated, and AMPK activity assay was performed. PEN2, AXIN1 and UHRF1 were investigated through gain/loss of function approaches, including overexpression, RNA interfering and CRISPR/Cas9-mediated gene knockout. Immunoprecipitation was utilized for detecting the interaction of UHRF1 and AMPKα1 after BBR treatment. Results: BBR activated lysosomal AMPK, but weaker than metformin. AXIN1 mediated BBR's effect on lysosomal AMPK activation, while PEN2 did not. BBR, but not metformin, decreased UHRF1 expression by promoting its degradation. BBR reduced the interaction between UHRF1 and AMPKα1. And overexpression of UHRF1 abolished the effect of BBR on AMPK activation. Conclusion: BBR activated lysosomal AMPK as dependent on AXIN1, but not PEN2. BBR maintained cellular AMPK activity by reducing UHRF1 expression and its interaction with AMPKα1. The mode of action of BBR was different from that of metformin on AMPK activation.

[Wernekink Commissure Syndrome With Hallucinations and Involuntary Groping:Report of One Case].

Wernekink commissure syndrome is a rare midbrain syndrome with bilateral cerebellar dysfunction,eye movement disorder,and palatal myoclonus.Few cases of this syndrome have been reported in China,let alone those combined with hallucinations and involuntary groping.This paper reports the diagnosis and treatment of a case of Wernekink commissure syndrome with hallucinations and involuntary groping,aiming to enrich the knowledge about this disease for clinicians.

Efficacy of new hemostatic techniques in nonvariceal gastrointestinal bleeding: A systematic review and network meta-analysis.

OBJECTIVES: Nonvariceal gastrointestinal bleeding (NVGIB) is a common medical condition with significant mortality and morbidity. Several types of hemostatic modalities are currently available in clinical setting. This systematic review and network meta-analysis aimed to assess the efficacy of these modalities in treating NVGIB. METHODS: PubMed, EMBASE, and the Cochrane Library databases were searched for studies that compared the efficacy of different hemostatic techniques (over-the-scope clip [OTSC], hemostatic powder [HP] and conventional endoscopic treatment [CET]) for NVGIB published up to June 2022. The 30-day rebleeding rate was regarded as the primary outcome. We performed pairwise and network meta-analyses for all treatments. The heterogeneity and transitivity were evaluated. RESULTS: Twenty-two studies were included. Regarding the 30-day rebleeding rate, OTSC and HP plus CET showed superior efficacy in treating NVGIB compared with CET (OTSC vs CET: relative risk [RR] 0.42, 95% confidence interval [CI] 0.28-0.60; HP plus CET vs CET: RR 0.40, 95% CI 0.17-0.87), while OTSC and HP plus CET had comparable efficacy (RR 0.95, 95% CI 0.38-2.31). HP plus CET ranked the highest in the network ranking estimate. The sensitivity analysis showed that it was not robust that OTSC was superior to CET regarding the short-term rebleeding rate and the initial hemostasis rate. While all-cause mortality, bleeding-related mortality and necessity of surgical or angiographic salvage therapy showed no statistically significant difference. CONCLUSION: OTSC and HP plus CET significantly reduced 30-day rebleeding rate compared to CET and had comparable efficacy in the treatment of NVGIB.

Effective detection of Ag+, Hg2+ and dye adsorption properties studies of Ln-MOFs based on a benzimidazole carboxylic acid ligand.

Five new lanthanide metal-organic frameworks (Ln-MOFs), namely {[Ln(L)]·Cl}n, [Ln = Pr(1), Nd(2), Eu(3), Ho(4), Ce(5)], based on a benzimidazole carboxylic acid ligand [H2L = 2-(2-carboxyphenyl)-1H-benzo[d]imidazole-6-carboxylic acid] were synthesized by a solvothermal method. Ln-MOFs 1-5 have the same two-dimensional layered structures. Interestingly, 1-5 exhibit excellent adsorption performance to anionic dye Congo red (CR), with adsorption capacities of 2724 mg g-1, 2719 mg g-1, 2718 mg g-1, 327 mg g-1, and 2273 mg g-1, respectively. Adsorption kinetics experiments showed that this kind of adsorption belonged to chemisorption; the hydrogen bonding and π-π interactions between the 1-5 host and CR guest molecules resulted in a high adsorption capacity. Luminescence and sensing experiments showed that 5 can be considered a promising multifunctional fluorescent sensor with good reusability and a high sensitivity toward Ag+ and Hg2+ ions, with detection limits of 1.7 × 10-7 and 2.5 × 10-6 M, respectively.

Berberine is a potential alternative for metformin with good regulatory effect on lipids in treating metabolic diseases.

Metformin (MTF) and berberine (BBR) share several therapeutic benefits in treating metabolic-related disorders. However, as the two agents have very different chemical structure and bioavailability in oral route, the goal of this study is to learn their characteristics in treating metabolic disorders. The therapeutic efficacy of BBR and MTF was systemically investigated in the high fat diet feeding hamsters and/or ApoE(-/-) mice; in parallel, gut microbiota related mechanisms were studied for both agents. We discovered that, although both two drugs had almost identical effects on reducing fatty liver, inflammation and atherosclerosis, BBR appeared to be superior over MTF in alleviating hyperlipidemia and obesity, but MTF was more effective than BBR for the control of blood glucose. Association analysis revealed that the modulation of intestinal microenvironment played a crucial role in the pharmacodynamics of both drugs, in which their respective superiority on the regulation of gut microbiota composition and intestinal bile acids might contribute to their own merits on lowering glucose or lipids. This study shows that BBR may be a good alternative for MTF in treating diabetic patients, especially for those complicated with dyslipidemia and obesity.

[Effect of Ganmai Dazao Decoction on ethology of rats with PTSD and its mechanism].

This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.

Dosimetry comparison with helical tomotherapy, volumetric modulated arc therapy, and intensity-modulated radiotherapy for grade II gliomas: A single­institution case series.

Radiotherapy is an essential postoperative treatment for grade II gliomas. However, comparative dosimetric studies of different radiotherapy plans for grade II gliomas are still lacking. Therefore, we conducted this case series analysis to compare the dosimetric differences among helical tomotherapy (TOMO), volumetric modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT) for grade II gliomas. To achieve that, seven diagnosed postoperative patients with grade II gliomas were analyzed by computed tomography and then planned with TOMO, VMAT, and IMRT. The plan target volume (PTV) prescribed dose was 50 Gy (daily fraction of 2.0 Gy, 5 days/week). The expected treatment efficiency was measured by monitor units (MUs) scoring. Treatment plans of the patients were compared in the quality of target volumes dosage coverage, the efficiency of dosage delivery, and the dosage exposure of normal adjacent organs at risk (OAR). Differences in each method were measured by utilizing the Nonparametric ANOVA. The study shows that TOMO achieved a significantly higher PTV-D98% (doses received by 98% of the PTV volume) than VMAT and IMRT (50.30 ± 0.13 vs 49.21 ± 0.19, p = 0.006; 50.30 ± 0.13 vs 49.78 ± 0.18, p = 0.014), while there was no difference in PTV-D2% (doses received by 2% of the PTV volume). IMRT achieved a conformity index (CI) preferably, and TOMO generated a favorable homogeneity index (HI) (p < 0.05 for both). The MUs were fewer for VMAT than IMRT and TOMO (294 ± 19, 572 ± 24, 317 ± 97, respectively). IMRT achieved better protection for the lens and brain stems. Our case series study indicated that TOMO, VMAT, and IMRT achieved a comparatively good target dosimetric coverage, and most OARs were protected well. IMRT is not inferior to TOMO and VMAT and is still very suitable for treating most grade II glioma patients.

Microbiota-derived short-chain fatty acids mediate the effects of dengzhan shengmai in ameliorating cerebral ischemia via the gut-brain axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengzhan shengmai (DZSM) formula, composed of four herbal medicines (Erigeron breviscapus, Panax ginseng, Schisandra chinensis, and Ophiopogon japonicus), is widely used in the recovery period of ischemic cerebrovascular diseases; however, the associated molecular mechanism remains unclear. AIM OF THE STUDY: The purpose of this study was to uncover the links between the microbiota-gut-brain axis and the efficacy of DZSM in ameliorating cerebral ischemic diseases. MATERIALS AND METHODS: The effects of DZSM on the gut microbiota community and bacteria-derived short-chain fatty acid (SCFA) production were evaluated in vivo using a rat model of cerebral ischemia and in vitro through the anaerobic incubation with fresh feces derived from model animals. Subsequently, the mechanism underlying the role of SCFAs in the DZSM-mediated treatment of cerebral ischemia was explored. RESULTS: We found that DZSM treatment significantly altered the composition of the gut microbiota and markedly enhanced SCFA production. The consequent increase in SCFA levels led to the upregulation of the expression of monocarboxylate transporters and facilitated the transportation of intestinal SCFAs into the brain, thereby inhibiting the apoptosis of neurocytes via the regulation of the PI3K/AKT/caspase-3 pathway. The increased intestinal SCFA levels also contributed to the repair of the 2VO-induced disruption of gut barrier integrity and inhibited the translocation of lipopolysaccharide from the intestine to the brain, thus attenuating neuroinflammation. Consequently, cerebral neuropathy and oxidative stress were significantly improved in 2VO model rats, leading to the amelioration of cerebral ischemia-induced cognitive dysfunction. Finally, fecal microbiota transplantation could reproduce the beneficial effects of DZSM on SCFA production and cerebral ischemia. CONCLUSIONS: Our findings suggested that SCFAs mediate the effects of DZSM in ameliorating cerebral ischemia via the gut microbiota-gut-brain axis.

[Diversity and functional prediction of gut microbiota in children with autism spectrum disorder]. / å­¤ç‹¬ç—‡è°±ç³»éšœç¢å„¿ç«¥è‚ é“èŒç¾¤å¤šæ ·æ€§ç ”ç©¶åŠåŠŸèƒ½é¢„æµ‹åˆ†æž.

OBJECTIVES: To study the structure and diversity of gut microbiota in children with autism spectrum disorder (ASD), and to predict the metabolic function of gut microbiota. METHODS: Fecal samples were collected from 30 ASD children (ASD group) and 20 typically developing (TD) children (TD group). Genomic DNA was extracted, the 16S rDNA V4 region was amplified by PCR, and Illumina NovaSeq6000 platform was used for high-throughput sequencing. The composition and distribution characteristics of gut microbiota were analyzed for the two groups, and the metabolic function of gut microbiota was predicted. RESULTS: There were no significant differences in alpha diversity indices (Chao1, Shannon, and Simpson) of gut microbiota between the ASD and TD groups (P>0.05). At the phylum and class levels, there was no significant difference in the structure of gut microbiota between the two groups (P>0.05). Compared with the TD group, the ASD group had significantly higher abundance of Megamonas, Barnesiella, Dialister, Megasphaera, Ruminococcus_torques_group, and Fusobacterium at the genus level (P<0.05). Functional prediction analysis showed that compared with the TD group, the ASD group had a significantly lower abundance of the gut microbiota with the metabolic functions such as tryptophan degradation, glutamate degradation, and butyrate production (P<0.05) and a significantly higher abundance of the gut microbiota with the metabolic function of GABA degradation (P<0.05). CONCLUSIONS: There is no significant difference in the alpha diversity of gut microbiota between ASD children and TD children, while there are differences in the composition of species at the genus level and the metabolic functions of gut microbiota.

Impact of glycemic gap on 30-day adverse outcomes in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND AND AIMS: Stress-induced hyperglycemia (SIH) generally occurs in critical illness. Recently, glycemic gap (GAP) has been considered to be a superior indicator of SIH. However, data on the association between GAP and prognosis in ST-segment elevation myocardial infarction (STEMI) is limited. This observational study aimed to estimate the prognostic value of GAPmean, defined as the difference between mean blood glucose level (MGL) within 24 h after admission and A1c-derived average glucose (ADAG), in patients with acute STEMI. METHODS: A total of 4952 patients with acute STEMI were included in the final analysis, and they were divided into four groups according to GAPmean quartiles and diabetes mellitus (DM). The primary outcomes were all-cause mortality and major adverse cardiovascular events (MACEs). Cox proportional hazards regression analysis and net reclassification improvement (NRI) analysis were performed. RESULTS: At 30 days of follow-up, 324 (6.5%) deaths and 569 (11.5%) MACEs occurred. With the elevation of GAPmean, the incidence of all-cause mortality (4.0%, 5.6%, 6.5%, and 10.1%) and MACEs (7.3%, 9.6%, 11.4%, and 17.7%) significantly increased. Receiver operating characteristic curve analysis demonstrated that GAPmean was superior to admission blood glucose (ABG) and GAPadm (defined as the difference between ABG and ADAG) to detect adverse outcomes. Multivariate Cox regression analysis revealed that elevated GAPmean was independently associated with all-cause death and MACEs. With the first quartile as a reference, the hazards ratios (HRs) for all-cause death in the second, third, and fourth quartiles were 1.49 (95% CI 1.02-2.18), 1.58 (95% CI 1.09-2.30), and 2.11 (95% CI 1.48-3.02), respectively, and the HRs for MACEs were 1.40 (95% CI 1.05-1.86), 1.60 (95% CI 1.21-2.11), and 2.17 (95% CI 1.66-2.83), respectively, which were independent of DM status. Continuous NRI analysis revealed that GAPmean significantly improved risk stratification for all-cause mortality and MACEs by 21.6% and 19.8%, respectively. CONCLUSIONS: The glycemic gap between MGL within 24 h after admission and ADAG was independently associated with 30-day all-cause mortality and MACEs in patients with acute STEMI, which was not affected by DM status. Further, the glycemic gap provided incremental accuracy in the risk stratification of STEMI.

PROM1 and CTGF Expression in Childhood MLL-Rearrangement Acute Lymphoblastic Leukemia.

The prognosis of over 90% of infant acute lymphoblastic leukemia (ALL) remains poor because of harboring the mixed-lineage leukemia gene (MLL) fusion. To give insight into the critical coexpressed genes related to the MLL-rearrangement (MLL-R) gene in childhood acute lymphoblastic leukemia, we integrated different bioinformatic methods. First, the gene expression data of MLL-R ALL and normal samples from GSE13159 and GSE13164 were analyzed using "compare" function in the Oncomine database. The top 150 overexpressed and 150 underexpressed genes were identified by the Oncomine website. Then, we employed the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) to define functional genes for the 300 DEGs. The Cytoscape identified two important networks for overexpressed genes, including 35 functional genes, among which PROM1, FLT3, CTGF, LGALS1, IGFBP7, ZNRF1, and RUNX2 were considered as the key genes because of their high expression in MLL-R ALL compared to the expression in other subclassification of leukemia in the MILE dataset. Further analysis of GSE68720, GSE19475, and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) ALL (phase I) database confirmed the robust expression of 7 key genes in MLL-R compared to MLL-germline (MLL-G) childhood ALL. Kaplan-Meier analysis indicated that childhood ALL patients with high PROM1 and CTGF expression had significantly poor overall survival. These findings suggest that PROM1 and CTGF represent two potential therapeutic targets for childhood MLL-R ALL.

Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model.

Chemoprevention of hepatocellular carcinoma (HCC) is highly desirable in clinic. Berberine (BBR) is reported to play potential roles in cancer treatment and prevention. We studied the chemopreventive effect of BBR on hepatocellular carcinogenesis in an inflammation-driven mouse model, as it was enriched in liver after oral administration. Oral BBR significantly decreased the number and volume of visible nodular tumors, and prolonged the median overall survival by 9 and 8 weeks in the diethylnitrosamine (DEN)-injected male and female mice respectively. The nodular tumors were induced through activation of the lysophosphatidic acid (LPA) pathway in liver. LPA stimulated the abnormal leptin transcription through interacting with LPA receptor-2 (LPAR2) followed by p38 activation, and BBR inhibited carcinogenesis by suppressing the bioactivity of LPA. Specifically, BBR significantly reduced the expression of the LPA synthetase autotaxin (ATX) and LPAR2 in the nodular tumors of DEN-injected mice. Subsequently, BBR repressed the abnormal transcription of leptin stimulated by LPA-induced phosphorylation of p38 in hepatoma cells. In fact, BBR reduced the abnormal expression of leptin in livers of DEN-injected male mice throughout the course of an 8-month experiment. BBR might be a preventive agent for HCC, working at least partially through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in liver.