Null and missense mutations of ERI1 cause a recessive phenotypic dichotomy in humans.

ERI1 is a 3'-to-5' exoribonuclease involved in RNA metabolic pathways including 5.8S rRNA processing and turnover of histone mRNAs. Its biological and medical significance remain unclear. Here, we uncover a phenotypic dichotomy associated with bi-allelic ERI1 variants by reporting eight affected individuals from seven unrelated families. A severe spondyloepimetaphyseal dysplasia (SEMD) was identified in five affected individuals with missense variants but not in those with bi-allelic null variants, who showed mild intellectual disability and digital anomalies. The ERI1 missense variants cause a loss of the exoribonuclease activity, leading to defective trimming of the 5.8S rRNA 3' end and a decreased degradation of replication-dependent histone mRNAs. Affected-individual-derived induced pluripotent stem cells (iPSCs) showed impaired in vitro chondrogenesis with downregulation of genes regulating skeletal patterning. Our study establishes an entity previously unreported in OMIM and provides a model showing a more severe effect of missense alleles than null alleles within recessive genotypes, suggesting a key role of ERI1-mediated RNA metabolism in human skeletal patterning and chondrogenesis.

High-Density Au Anchored to Ti3C2-Based Colorimetric-Fluorescence Dual-Mode Lateral Flow Immunoassay for All-Domain-Enhanced Performance and Signal Intercalibration.

In this work, a novel MXene-Au nanoparticle (Ti3C2@Au) was synthesized with a high molar extinction coefficient, strong fluorescence quenching ability, ultrahigh antibody affinity, high stability, and good dispersibility, and it was used to develop a colorimetric-fluorescence dual-mode lateral flow immunoassay (LFIA). The detection limits of this method for the detection of dexamethasone in milk, beef, and pork were 0.0018, 0.12, and 0.084 µg/kg in the "turn-off" mode (colorimetric signal), and 0.0013, 0.080, and 0.070 µg/kg in the "turn-on" mode (fluorescent signal), respectively, which was up to 231-fold more sensitive compared with that of the reported LFIAs. The recovery rates ranged from 81.1-113.7%, and 89.2-115.4%, with the coefficients of variation ranging from 1.4-15.0%, and 1.9-14.8%, respectively. The results of the LC-MS/MS confirmation test on 30 real samples had a good correlation with that of our established method (R2 > 0.97). This work not only developed novel nanocarriers for antibody-based LFIA but also ensured high-performance detection.

Time transfer over 113†km free space laser communication channel.

The space time frequency transfer plays a crucial role in applications such as space optical clock networks, navigation, satellite ranging, and space quantum communication. Here, we propose a high-precision space time frequency transfer and time synchronization scheme based on a simple intensity modulation/direct detection (IM/DD) laser communication system, which occupies a communication bandwidth of approximately 0.2%. Furthermore, utilizing an optical-frequency comb time frequency transfer system as an out-of-loop reference, experimental verification was conducted on a 113 km horizontal atmospheric link, with a long-term stability approximately 8.3 × 10-16 over a duration of 7800 seconds. Over an 11-hour period, the peak-to-peak wander is approximately 100 ps. Our work establishes the foundation of the time frequency transfer, based on the space laser communication channel, for future ground-to-space and inter-satellite links.

Deciphering the Roles of Extracellular Polymeric Substances (EPS) in Shaping Disinfection Kinetics through Permanent Removal via Genetic Disruption.

Extracellular polymeric substances (EPS) ubiquitously encapsulate microbes and play crucial roles in various environmental processes. However, understanding their complex interactions with dynamic bacterial behaviors, especially during the disinfection process, remains very limited. In this work, we investigated the impact of EPS on bacterial disinfection kinetics by developing a permanent EPS removal strategy. We genetically disrupted the synthesis of exopolysaccharides, the structural components of EPS, in Pseudomonas aeruginosa, a well-known EPS-producing opportunistic pathogen found in diverse environments, creating an EPS-deficient strain. This method ensured a lasting absence of EPS while maintaining bacterial integrity and viability, allowing for real-time in situ investigations of the roles of EPS in disinfection. Our findings indicate that removing EPS from bacteria substantially lowered their susceptibility threshold to disinfectants such as ozone, chloramine B, and free chlorine. This removal also substantially accelerated disinfection kinetics, shortened the resistance time, and increased disinfection efficiency, thereby enhancing the overall bactericidal effect. The absence of EPS was found to enhance bacterial motility and increase bacterial cell vulnerability to disinfectants, resulting in greater membrane damage and intensified reactive oxygen species (ROS) production upon exposure to disinfectants. These insights highlight the central role of EPS in bacterial defenses and offer promising implications for developing more effective disinfection strategies.

[Deficiency of cathepsin K improves ischemic angiogenesis in high-fat diet fed mice].

The present study aims to investigate the effect of cathepsin K (CatK) on ischemic angiogenesis in high-fat diet fed mice. The mice were subjected to unilateral hindlimb ischemic surgery, and the ischemic blood flow was measured with a laser Doppler blood flow imager. Immunohistochemical staining was used to observe the quantity of new capillaries in the ischemic lower extremity, and Western blot was used to detect the expression of insulin receptor substrate-1 (IRS-1), p-Akt, Akt and vascular endothelial growth factor (VEGF). Firstly, the effect of high-fat diet on ischemic angiogenesis was observed in wild-type mice, which were randomly divided into control group and high-fat diet group and were fed with normal diet or 60% high-fat diet respectively for 16 weeks. The results showed the body weight and the plasma CatK concentration of the high-fat diet group was significantly increased compared with the control group (P < 0.05), and the blood flow recovery of the high-fat diet group was significantly lower than control group (P < 0.05). Then, wild-type and CatK knock out (CatK-/-) mice were both fed with high-fat diet to further observe the effect and mechanism of CatK on ischemic angiogenesis under high-fat diet. The results showed that the blood flow recovery in the CatK-/- group was significantly greater than the wild-type group, and the number of CD31 positive cells was significantly increased (P < 0.05). At the same time, the protein expression levels of IRS-1, p-Akt and VEGF in the ischemic skeletal muscle were significantly increased in the CatK-/- group compared with the wild-type group (P < 0.05). These results suggest that the deficiency of CatK improves ischemic angiogenesis in high-fat diet fed mice through IRS-1-Akt-VEGF signaling pathway.

Enhancing Ionic Selectivity and Osmotic Energy by Using an Ultrathin Zr-MOF-Based Heterogeneous Membrane with Trilayered Continuous Porous Structure.

Designing a nanofluidic membrane with high selectivity and fast ion transport property is the key towards high-performance osmotic energy conversion. However, most of reported membranes can produce power density less than commercial benchmark (5 W/m2), due to the imbalance between ion selectivity and permeability. Here, we report a novel nanoarchitectured design of a heterogeneous membrane with an ultrathin and dense zirconium-based UiO-66-NH2 metal-organic framework (MOF) layer and a highly aligned and interconnected branched alumina nanochannel membrane. The design leads to a continuous trilayered pore structure of large geometry gradient in the sequence from angstrom-scale to nano-scale to sub-microscale, which enables the enhanced directional ion transport, and the angstrom-sized (~6.6-7 Å) UiO-66-NH2 windows render the membrane with high ion selectivity. Consequently, the novel heterogeneous membrane can achieve a high-performance power of ~8 W/m2 by mixing synthetic seawater and river water. The power density can be largely upgraded to an ultrahigh ~17.1 W/m2 along with ~48.5 % conversion efficiency at a 50-fold KCl gradient. This work not only presents a new membrane design approach but also showcases the great potential of employing the zirconium-based MOF channels as ion-channel-mimetic membranes for highly efficient blue energy harvesting.

A Comparative Study of Prevalence and Associated Factors of Social Support Among Chinese Shidu Parents and Non-Shidu Parents.

The number of parents in China who have lost their only child, referred to as shidu parents, currently exceeds one million and is increasing by approximately 76,000 annually. Shidu parents face a unique challenge in long-term care, primarily stemming from the sudden and tragic loss of their only child, which leads to a substantial decrease in their social support network. A multi-stage, stratified, and cluster sampling method was employed across various economic belts. Linear regression analysis was utilized to examine factors associated with the social support status of shidu and non-shidu parents. The level of social support decreases as the severity of depression increases. Shidu parents with grandchildren tend to have good social support. The city of Hangzhou exhibits relatively high levels of social support. Married individuals typically report higher levels of social support. It is recommended to prioritize shidu parents without grandchildren as a primary focus for government and societal support. Key recommendations include strengthening social skills training and developing social support networks. Drive economic development, particularly in relatively underdeveloped regions. Strengthen social organizations and community development. Enhancing access to support services, leveraging technology, and encouraging volunteerism for non-married parents.

An Artificial Enzyme for Asymmetric Nitrocyclopropanation of α,ß-Unsaturated Aldehydes-Design and Evolution.

The introduction of an abiological catalytic group into the binding pocket of a protein host allows for the expansion of enzyme chemistries. Here, we report the generation of an artificial enzyme by genetic encoding of a non-canonical amino acid that contains a secondary amine side chain. The non-canonical amino acid and the binding pocket function synergistically to catalyze the asymmetric nitrocyclopropanation of α,ß-unsaturated aldehydes by the iminium activation mechanism. The designer enzyme was evolved to an optimal variant that catalyzes the reaction at high conversions with high diastereo- and enantioselectivity. This work demonstrates the application of genetic code expansion in enzyme design and expands the scope of enzyme-catalyzed abiological reactions.

Simultaneous Determination of Rifamycin Antibiotics and Their Active Metabolites in Human Plasma Using UHPLC-MS/MS to Evaluate Their Impact on Target Peak Concentrations: A Short Communication.

BACKGROUND: Standard and proper antituberculosis (anti-TB) treatment is essential for patients with TB, and rifamycin antibiotics are key components of anti-TB therapy. Therapeutic drug monitoring (TDM) of rifamycin antibiotics can shorten the time to response and complete treatment of TB. Notably, antimicrobial activities of the major active metabolites of rifamycin are similar to those of their parent compounds. Thus, a rapid and simple assay was developed for simultaneous determination of rifamycin antibiotics and their major active metabolites in plasma to evaluate their impact on target peak concentrations. Here, the authors have developed and validated a method for simultaneous determination of rifamycin antibiotics and their active metabolites in human plasma using ultrahigh-performance liquid chromatography tandem mass spectrometry. METHODS: Analytical validation of the assay was performed in accordance with the bioanalytical method validation guidance for industry described by the US Food and Drug Administration and the guidelines for bioanalytical method validation described by the European Medicines Agency. RESULTS: The drug concentration quantification method for rifamycin antibiotics, including rifampicin, rifabutin, and rifapentine, and their major active metabolites was validated. Significant differences in the proportions of active metabolites in rifamycin antibiotics may affect the redefinition of their effective concentration ranges in the plasma. The method developed herein is expected to redefine the ranges of "true" effective concentrations of rifamycin antibiotics (including parent compounds and their active metabolites). CONCLUSIONS: The validated method can be successfully applied for high-throughput analysis of rifamycin antibiotics and their active metabolites for TDM in patients receiving anti-TB treatment regimens containing these antibiotics. Proportions of active metabolites in rifamycin antibiotics markedly varied among individuals. Depending on the clinical indications of patients, the therapeutic ranges for rifamycin antibiotics may be redefined.

How to adjust the expected waiting time to improve patient's satisfaction?

BACKGROUND: Long waiting time in hospital leads to patient's low satisfaction. In addition to reducing the actual waiting time (AWT), we can also improve satisfaction by adjusting the expected waiting time (EWT). Then how much can the EWT be adjusted to attribute a higher satisfaction? METHODS: This study was conducted though experimental with hypothetical scenarios. A total of 303 patients who were treated by the same doctor from August 2021 to April 2022 voluntarily participated in this study. The patients were randomly divided into six groups: a control group (n = 52) and five experimental groups (n = 245). In the control group, the patients were asked their satisfaction degree regarding a communicated EWT (T0) and AWT (Ta) under a hypothetical situation. In the experimental groups, in addition to the same T0 and Ta as the control group, the patients were also asked about their satisfaction degree with the extended communicated EWT (T1). Patients in five experimental groups were given T1 values with 70, 80, 90, 100, and 110 min respectively. Patients in both control and experiment groups were asked to indicate their initial EWT, after given unfavorable information (UI) in a hypothetical situation, the experiment groups were asked to indicate their extended EWT. Each participant only participated in filling out one hypothetical scenario. 297 valid hypothetical scenarios were obtained from the 303 hypothetical scenarios given. RESULTS: The experimental groups had significant differences between the initial indicated EWT and extended indicated EWT under the effect of UI (20 [10, 30] vs. 30 [10, 50], Z = -4.086, P < 0.001). There was no significant difference in gender, age, education level and hospital visit history (χ2 = 3.198, P = 0.270; χ2 = 2.177, P = 0.903; χ2 = 3.988, P = 0.678; χ2 = 3.979, P = 0.264) in extended indicated EWT. As for patient's satisfaction, compared with the control group, significant differences were found when T1 = 80 min (χ2 = 13.511, P = 0.004), T1 = 90 min (χ2 = 12.207, P = 0.007) and T1 = 100 min (χ2 = 12.941, P = 0.005). When T1 = 90 min, which is equal to the Ta, 69.4% (34/49) of the patients felt "very satisfied", this proportion is not only significantly higher than that of the control group (34/ 49 vs. 19/52, χ2 = 10.916, P = 0.001), but also the highest among all groups. When T1 = 100 min (10 min longer than Ta), 62.5% (30/48) of the patients felt "very satisfied", it is significantly higher than that of the control group (30/ 48 vs. 19/52, χ2 = 6.732, P = 0.009). When T1 = 80 min (10 min shorter than Ta), 64.8% (35/54) of the patients felt "satisfied", it is significantly higher than that of the control group (35/ 54 vs. 17/52, χ2 = 10.938, P = 0.001). However, no significant difference was found when T1 = 70 min (χ2 = 7.747, P = 0.052) and T1 = 110 min (χ2 = 4.382, P = 0.223). CONCLUSIONS: Providing UI prompts can extend the EWT. When the extended EWT is closer to the AWT, the patient's satisfaction level can be improved higher. Therefore, medical institutions can adjust the EWT of patient's through UI release according to the AWT of hospitals to improve patient's satisfaction.

Clinical Value Analysis of Serum TK1, SCC-Ag, and MUC-1 in the Diagnosis and Prognosis Evaluation of Cervical Cancer.

Objective: This study aims to analyze the diagnostic and prognostic value of serum thymidine kinase (TK1), squamous cell carcinoma antigen (SCC-Ag), and mucin-1 (MUC-1) in cervical cancer. Methods: This retrospective study included 85 cervical cancer patients as the experimental group treated at our hospital's obstetrics and gynecology department from January 2016 to January 2019. The benign group also consisted of 85 patients with benign lesions treated during the same period, and the comparison group comprised 85 patients with healthy physical examinations at the same time. Results: Serum levels of TK1, SCC-Ag, and MUC-1 were significantly higher in the experimental group than in the benign group and higher in the benign group than in the comparison group (P < .05). Additionally, serum TK1, SCC-Ag, and MUC-1 were higher in the lymph node metastasis group, infiltration depth > 1/2 group, tumor diameter ≥ 4 cm group, and stage III-IV group compared to the non-lymph node metastasis group, infiltration depth ≤ 1/2 group, tumor diameter <4 cm group, and stage I-II group (P < .05). No significant differences in serum TK1, SCC-Ag, and MUC-1 among different pathological types and age groups (P > .05). Moreover, serum TK1, SCC-Ag, and MUC-1 levels were higher in the deceased group compared to the survivor group (P < .05). These markers were negatively correlated with survival time (r value = -0.524, -0.428, -0.516), indicating that as the severity of cervical cancer increased, serum TK1, SCC-Ag, and MUC-1 concentrations also increased. The levels of these markers were significantly higher in deceased patients compared to survivors. Conclusions: Serum levels of TK1, SCC-Ag, and MUC-1 show promise as biomarkers for cervical cancer diagnosis and prognosis. TK1 and SCC-Ag are elevated, while MUC-1 is decreased in cervical cancer patients. Further research is warranted to confirm these findings and explore additional biomarkers.

Extraction and characterization of anti-virus anthraquinones from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220.

In this study, seven novel anthraquinones (1-7) and four described anthraquinones (8-11) were purified from Nicotiana tabacum-derived Aspergillus oryzae YNCA1220. It is worth noting that only analogs of 4 and 5 have been reported as natural products to date, while the nuclei of compounds 1-3, 6 and 7 were isolated for the first time in nature. Among them, compounds 1-3 bear an unusual anthra[2,3-b]furan-9,10-dione nucleus, 4 and 5 possess a rare 3-methyl-1H-pyrrol-2-yl substituent, and 6 and 7 are new framework anthraquinones bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. Interestingly, the in vivo assays indicated that 1, 4 and 5 had inactivation effects against tobacco mosaic virus (TMV) with inhibition rates of 41.6%, 55.4% and 38.6%, respectively, at a concentration of 50 µg/mL, which were better than that of the positive control agent, ningnanmycin (33.8%). Compounds 1, 4 and 5 also had protective effects with inhibition rates of 48.7%, 60.2% and 43.5% at the same concentration, while 4 had a better curative effect than ningnanmycin at a concentration of 100 µg/mL. In addition, mechanistic studies also revealed that a potent direct effect on TMV, the induction of SAR in tobacco plants, and the effective regulation of defense enzymes, defense genes, and defense hormones may be the reasons for the significant effects of 4 against TMV. At the same time, downregulation of the expression of total NtHsp70 protein by inhibiting the related Hsp70 genes may also be involved in tobacco resistance to TMV. To evaluate whether compounds have broader antiviral activities, the antirotavirus activities of new isolates were also evaluated and found to be highly effective with a therapeutic index (TI) value ranging from 11.6 to 17.7. This study suggests that the above anthraquinone compounds, particularly 4, have broad spectrum antiviral activities. The successful isolation and structure identification of the above anthraquinones provide new materials for the screening of anti-TMV agents and contribute to the improved utilization of N. tabacum-derived fungi.

Electron-Rich Triazine-Conjugated Microporous Polymers for the Removal of Dyes from Wastewater.

Conjugated microporous polymers (CMP) as porous functional materials have received considerable attention due to their unique structures and fascinating properties for the adsorption and degradation of dyes. Herein, a triazine-conjugated microporous polymer material with rich N-donors at the skeleton itself was successfully synthesized via the Sonogashira-Hagihara coupling by a one-pot reaction. These two polymers had Brunauer-Emmett-Teller (BET) surface areas of 322 and 435 m2g-1 for triazine-conjugated microporous polymers (T-CMP) and T-CMP-Me, respectively. Due to the porous effects and the rich N-donor at the framework, it displayed a higher removal efficiency and adsorption performance compared to cationic-type dyes and selectivity properties for (methylene blue) MB+ from a mixture solution of cationic-type dyes. Furthermore, the T-CMP-Me could quickly and drastically separate MB+ and (methyl orange) MO- from the mixed solution within a short time. Their intriguing absorption behaviors are supported by 13C NMR, UV-vis absorption spectroscopy, scanning electron microscopy, and X-ray powder diffraction studies. This work will not only improve the development of porous material varieties, but also demonstrate the adsorption or selectivity of porous materials for dyes from wastewater.

[Glycosylphosphatidylinositol biosynthesis deficiency 15 caused by GPAA1 gene mutation: a rare disease study]. / ç½•è§ç— ç ”ç©¶ï¼šGPAA1åŸºå› çªå˜å¯¼è‡´ç³–åŸºç£·è„‚é °è‚Œé†‡ç”Ÿç‰©åˆæˆç¼ºé™·15型.

A boy, aged 6 years, attended the hospital due to global developmental delay for 6 years and recurrent fever and convulsions for 5 years. The boy was found to have delayed mental and motor development at the age of 3 months and experienced recurrent fever and convulsions since the age of 1 year, with intermittent canker sores and purulent tonsillitis. During the fever period, blood tests showed elevated white blood cell count, C-reactive protein, and erythrocyte sedimentation rate, which returned to normal after the fever subsides. Electroencephalography showed epilepsy, and genetic testing showed compound heterozygous mutations in the GPAA1 gene. The boy was finally diagnosed with glycosylphosphatidylinositol biosynthesis deficiency 15 (GPIBD15) and periodic fever. The patient did not respond well to antiepileptic treatment, but showed successful fever control with glucocorticoid therapy. This article reports the first case of GPIBD15 caused by GPAA1 gene mutation in China and summarizes the genetic features, clinical features, diagnosis, and treatment of this disease, which provides a reference for the early diagnosis and treatment of GPIBD15.

Biosynthesis of Tasikamides via Pathway Coupling and Diazonium-Mediated Hydrazone Formation.

Naturally occurring hydrazones are rare despite the ubiquitous usage of synthetic hydrazones in the preparation of organic compounds and functional materials. In this study, we discovered a family of novel microbial metabolites (tasikamides) that share a unique cyclic pentapeptide scaffold. Surprisingly, tasikamides A-C (1-3) contain a hydrazone group (C═N─N) that joins the cyclic peptide scaffold to an alkyl 5-hydroxylanthranilate (AHA) moiety. We discovered that the biosynthesis of 1-3 requires two discrete gene clusters, with one encoding a nonribosomal peptide synthetase (NRPS) pathway for assembling the cyclic peptide scaffold and another encoding the AHA-synthesizing pathway. The AHA gene cluster encodes three ancillary enzymes that catalyze the diazotization of AHA to yield an aryl diazonium species (diazo-AHA). The electrophilic diazo-AHA undergoes nonenzymatic Japp-Klingemann coupling with a ß-keto aldehyde-containing cyclic peptide precursor to furnish the hydrazone group and yield 1-3. The studies together unraveled a novel mechanism whereby specialized metabolites are formed by the coupling of two biosynthetic pathways via an unprecedented in vivo Japp-Klingemann reaction. The findings raise the prospect of exploiting the arylamine-diazotizing enzymes (AAD) for the in vivo synthesis of aryl compounds and modification of biological macromolecules.

Regular Use of Proton Pump Inhibitor and the Risk of Inflammatory Bowel Disease: Pooled Analysis of 3 Prospective Cohorts.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) have a major impact on gut microbiome and immune function, which in turn, may increase the risk of inflammatory bowel disease (IBD). Our aim in this study was to evaluate PPI use and subsequent risk of IBD and subtypes (ie, Crohn's disease and ulcerative colitis). METHODS: This was a pooled analysis of the Nurses' Health Study (NHS, n = 82,869), NHS II (n = 95,141), and UK Biobank (n = 469,397). We included participants with information on personal use of PPIs and free of IBD or cancer at baseline. We evaluated hazard ratios and 95% confidence intervals (CIs) with Cox regression adjusting for lifestyle factors, PPI indications, comorbidities, and other medications. RESULTS: We documented 271 cases of IBD (median follow-up, 12 years) in the pooled NHS cohorts and 1419 cases (median follow-up, 8.1 years) in the UK Biobank. For both pooled NHS cohorts and UK Biobank, regular use of PPIs consistently showed a significantly positive association with IBD, Crohn's disease, and ulcerative colitis risk. Combined analyses of 3 cohorts showed that regular PPI users had an increased risk of IBD as compared with nonusers (hazard ratio, 1.42; 95% CI, 1.22-1.65; number needed to harm, 3770; 95% CI, 3668-4369). Direct comparison with H2 receptor antagonist, a less potent acid suppressor, showed that PPI use was also associated with higher IBD risk (hazard ratio, 1.38; 95% CI, 1.16-1.65). CONCLUSIONS: Regular use of PPIs was associated with an increased risk of IBD and its subtypes. The findings should be interpreted with caution because the absolute risk was low and the clinical benefits of PPIs are substantial.

ATF2 accelerates the invasion and metastasis of hepatocellular carcinoma through targeting the miR-548p/TUFT1 axis.

AIM: Due to high invasion and metastasis, hepatocellular carcinoma (HCC) is known as one of the most fatal carcinomas. We aim to further investigate regulatory mechanisms of invasion and metastasis to elucidate HCC pathogenesis and develop novel medications. METHODS: Patient specimens were collected for assessing gene expression and correlation between gene expressions. The expression of Ki67 and E-cadherin in subcutaneous xenograft tumor were examined by immunohistochemistry staining. The expression of activating transcription factor 2 (ATF2), miR-548p and TUFT1 were determined using Real-time quantitative reverse transcription polymerase chain reaction. Epithelial-mesenchymal transition and PI3K/AKT signaling-associated markers were examined with western blot. The proliferation, migration and invasion were assessed by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide, colony formation and transwell assays, respectively. Cell apoptosis was assessed via Annexin V and propidium iodide staining. Gene interaction was confirmed using chromatin immunoprecipitation and luciferase activity assays. Subcutaneous and intravenous xenograft mouse models were established for analyzing HCC growth and metastasis in vivo. RESULTS: ATF2 was up-regulated in HCC patients and cells. ATF2 promoted HCC cell proliferation, migration and invasion and inhibited cell apoptosis through directly targeting miR-548p and controlling its expression. miR-548p suppressed HCC cell proliferation, migration and invasion and enhanced cell apoptosis. miR-548p directly bound to the 3'UTR of TUFT1 to restrain its expression and subsequently suppress the PI3K/AKT signaling. ATF2 knock-down significantly suppressed the growth and metastasis of HCC. CONCLUSION: ATF2 accelerates HCC progression by promoting cell proliferation, migration, invasion and metastasis, which is dependent on regulating the miR-548p/TUFT1 axis.

Optical weak measurement for the precise thickness determination of an ultra-thin film.

A total internal reflection system based on the weak value amplification principle is set up for the precise measurement of the thickness of an ultra-thin film. In this system, the film thickness is derived from the change of the double-peak pointer caused by the effective refractive index of the film, which is correlated to its thickness. The sensitivity and resolution of this system reached 2727.21 nm/RIU and 7.2×10-6 R I U, respectively, determined by using a sodium chloride solution with a refractive index of 1.331911. The growth process of TA/Fe(III) assembled films with thicknesses in the few nanometers range is monitored using the as-set-up system, and the experimental results are consistent with a theoretical calculation based on the Maxwell Garnett effective medium. Additionally, we theoretically calculated the detection limit for the thickness measurement of the film as 22 pm. We clearly provide a potential method for the precise measurement of the thickness of an ultra-thin film.

Protective effect of methionine on the intestinal oxidative stress and microbiota change induced by nickel.

Nickel is a common heavy metal pollutant in industrial areas and can cause oxidative damage to human and animal organs. As an essential amino acid with antioxidant function, methionine (Met) may protect the body from the oxidative stress induce by nickel, however, there is not enough research to study in this aspect. The study aims at investigating the effect of Met on the nickel-induced intestinal oxidative stress and further detected the gut microbiota changes. Mice were gavaged with quantitative NiCl2 (1.6 mg/ml, 0.25 ml) and fed with different doses of methionine in each group. The contents of intestinal oxidation product and antioxidant enzymes were determined by different biochemical quantitative methods, and the data showed that NiCl2 increased the content of intestinal oxidation product (MDA), and the antioxidant enzymes (GSH-Px, GR, SOD and CAT) were decreased. But this situation was alleviated in the group fed with additional methionine solution (0.5 mg/ml). In addition, we detected changes in the gut microbiota using high-throughput sequencing, the results showed that the structure of intestinal flora was disturbed by NiCl2, but methionine restored the germs with antioxidant capacity. Based on the results, we speculate that methionine can alleviate the impact of NiCl2 on the intestinal by enhancing the activity of antioxidant enzymes and the number of gut bacteria with anti-oxidation, suggesting that methionine as a nutritional additive may have the potential to treat nickel poisoning.

Effect of goal-directed fluid therapy on renal function in critically ill patients: a systematic review and meta-analysis.

OBJECTIVE: To evaluate whether goal-directed fluid therapy (GDFT) reduces the risk of renal injury in critical illness. METHODS: MEDLINE via PubMed, EMBASE, CENTRAL and CBM was searched from inception to 13 March 2022, for studies comparing the effect of GDFT with usual care on renal function in critically ill patients. GDFT was defined as a protocolized intervention based on hemodynamic and/or oxygen delivery parameters. A fixed or random effects model was applied to calculate the pooled odds ratio (OR) based on heterogeneity through the included studies. RESULTS: A total of 28 studies with 9,019 patients were included. The pooled data showed that compared with usual care, GDFT reduced the incidence of acute kidney injury (AKI) in critical illness (OR 0.62, 95% confidence interval (CI) 0.47 to 0.80, p< 0.001). Sensitivity analysis with only low risk of bias studies showed the same result. Subgroup analyses found that GDFT was associated with a lower AKI incidence in both postoperative and medical patients. The reduction was significant in GDFT aimed at dynamic indicators. However, no significant difference was found between groups in RRT support (OR 0.88, 95% CI 0.74 to 1.05, p= 0.17). GDFT tended to increase fluid administration within the first 6 h, decrease fluid administration after 24 h, and was associated with more vasopressor requirements. CONCLUSIONS: This meta-analysis suggests that GDFT aimed at dynamic indicators may be an effective way to prevent AKI in critical illness. This may indicate a benefit from early adequate fluid resuscitation and the combined effect of vasopressors.