Golgi-to-ER retrograde transport prevents premature differentiation of Drosophila type II neuroblasts via Notch-signal-sending daughter cells.

Stem cells are heterogeneous to generate diverse differentiated cell types required for organogenesis; however, the underlying mechanisms that differently maintain these heterogeneous stem cells are not well understood. In this study, we identify that Golgi-to-endoplasmic reticulum (ER) retrograde transport specifically maintains type II neuroblasts (NBs) through the Notch signaling. We reveal that intermediate neural progenitors (INPs), immediate daughter cells of type II NBs, provide Delta and function as the NB niche. The Delta used by INPs is mainly produced by NBs and asymmetrically distributed to INPs. Blocking retrograde transport leads to a decrease in INP number, which reduces Notch activity and results in the premature differentiation of type II NBs. Furthermore, the reduction of Delta could suppress tumor formation caused by type II NBs. Our results highlight the crosstalk between Golgi-to-ER retrograde transport, Notch signaling, stem cell niche, and fusion as an essential step in maintaining the self-renewal of type II NB lineage.

Identification and Experimental Validation of LINC00582 Associated with B Cell Immune and Development of Pulpitis: Bioinformatics and In Vitro Analysis.

BACKGROUND: Pulpitis is a common oral disease. Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) can regulate the immune response in pulpitis. This study focused on finding the key immune-related lncRNAs that regulate the development of pulpitis. METHODS: Differentially expressed lncRNAs were analyzed. Enrichment analysis was performed to explore the function of differentially expressed genes. Immune cell infiltration was evaluated with Immune Cell Abundance Identifier. Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase release assays were conducted to measure the viability of human dental pulp cells (HDPCs) and BALL-1 cells. Transwell assay was processed to prove migration and invasion of BALL-1 cells. RESULTS: Our results revealed that 17 lncRNAs were significantly upregulated. Pulpitis-related genes were mainly enriched in inflammatory relative signal pathways. The abundance of various immune cells was significantly abnormal in pulpitis tissues, among which the expression of eight lncRNAs was significantly correlated with the expression of B cell marker protein CD79B. As the most relevant lncRNA for B cells, LINC00582 could regulate the proliferation, migration, invasion, and CD79B expression of BALL-1 cells. CONCLUSIONS: Our study identified eight B cell immune-related lncRNAs. Meanwhile, LINC00582 has a positive effect on B cell immunity in the development of pulpitis.

Rhabdomyolysis in a male adolescent associated with monotherapy of fluvoxamine.

Rhabdomyolysis is a syndrome resulting from striated muscular breakdown, which may occur due to drug therapy with agents such as selective serotonin reuptake inhibitors (SSRIs). Although studies have shown that fluvoxamine can rarely cause myalgia, there are no reported cases of rhabdomyolysis due to fluvoxamine monotherapy. Here we describe a case of rhabdomyolysis due to fluvoxamine monotherapy for obsessive-compulsive disorder. The young adolescent developed pain in the extremities, and an increase in serum creatine kinase (CK) and myoglobin during fluvoxamine treatment. These adverse reactions were reversed immediately after the medicine was changed to another SSRI-sertraline. This is the first reported case of fluvoxamine-associated rhabdomyolysis. It is advisable to determine serum CK levels before starting fluvoxamine treatment, and then at regular intervals, to avoid the occurrence of severe acute kidney injury with possible life-threatening complications.

Nitric oxide alleviates salt stress through protein S-nitrosylation and transcriptional regulation in tomato seedlings.

MAIN CONCLUSION: NO enhances the resistance of tomato seedlings to salt stress through protein S-nitrosylation and transcriptional regulation, which involves the regulation of MAPK signaling and carbohydrate metabolism. Nitric oxide (NO) regulates various physiological and biochemical processes and stress responses in plants. We found that S-nitrosoglutathione (GSNO) treatment significantly promoted the growth of tomato seedling under NaCl stress, indicating that NO plays a positive role in salt stress resistance. Moreover, GSNO pretreatment resulted in an increase of endogenous NO level, S-nitrosothiol (SNO) content, S-nitrosoglutathione reductase (GSNOR) activity and GSNOR expression under salt stress, implicating that S-nitrosylation might be involved in NO-alleviating salt stress. To further explore whether S-nitrosylation is a key molecular mechanism of NO-alleviating salt stress, the biotin-switch technique and liquid chromatography/mass spectrometry/mass spectrometry (LC-MS/MS) were conducted. A total of 1054 putative S-nitrosylated proteins have been identified, which were mainly enriched in chloroplast, cytoplasm and mitochondrion. Among them, 15 and 22 S-nitrosylated proteins were involved in mitogen-activated protein kinase (MAPK) signal transduction and carbohydrate metabolism, respectively. In MAPK signaling, various S-nitrosylated proteins, SAM1, SAM3, SAM, PP2C and SnRK, were down-regulated and MAPK, MAPKK and MAPKK5 were up-regulated at the transcriptional level by GSNO treatment under salt stress compared to NaCl treatment alone. The GSNO pretreatment could reduce ethylene production and ABA content under NaCl stress. In addition, the activities of enzyme identified in carbohydrate metabolism, their expression at the transcriptional level and the metabolite content were up-regulated by GSNO supplication under salt stress, resulting in the activation of glycolysis and tricarboxylic acid cycle (TCA) cycles. Thus, these results demonstrated that NO might beneficially regulate MAPK signaling at transcriptional levels and activate carbohydrate metabolism at the post-translational and transcriptional level, protecting seedlings from energy deficiency and salinity, thereby alleviating salt stress-induced damage in tomato seedlings. It provides initial insights into the regulatory mechanisms of NO in response to salt stress.

Trends and Correlation Between Antimicrobial Resistance and Antibiotics Consumption in a Specialist Children's Hospital from 2016 to 2021.

Purpose: To explore the trends and correlation between antibiotics consumption and antimicrobial resistance in children in a specialist hospital from 2016-2021 in China. Patients and Methods: This retrospective study investigated data on the consumption of antibiotics and antimicrobial resistance in children. Antibiotics consumption was expressed as defined daily doses (DDDs)/1000 patient-days based on the Guidelines for Anatomical Therapeutic Chemical. The trends in antibiotics consumption and antimicrobial resistance rates were analyzed by linear regression, while Spearman correlation analysis was employed to evaluate their correlations. Results: An increasing trend in the annual consumption of carbapenems and monobactams was detected (all P<0.05). A significant upward trend was detected in the annual resistance rates of Enterococcus faecium to ciprofloxacin, Streptococcus pneumonia to ceftriaxone, Acinetobacter baumannii to carbapenems, Enterobacter cloacae to carbapenems, Pseudomonas aeruginosa to ceftazidime, and Escherichia coli to cefepime, while the annual resistance rates of Escherichia coli to carbapenems had a significant downward trend (all P<0.05). The consumption of cephalosporin/ß-lactamase inhibitor (C/BLI) combinations and carbapenems had significant positive correlations with the resistance rates of Acinetobacter baumannii to carbapenems (r=0.763, P<0.001; r=0.806, P<0.001), Enterobacter cloacae to carbapenems (r=0.675, P<0.001; r=0.417, P=0.043), and Pseudomonas aeruginosa to ceftazidime (r=0.625, P=0.001; r=0.753, P<0.001), respectively. Also, increasing consumption of monobactams was related to the upward resistance rates of Acinetobacter baumannii to carbapenems (r=0.557, P=0.005) and Enterobacter cloacae to carbapenems (r=0.507, P= 0.011). Conclusion: This study demonstrated significant positive associations between antibiotics consumption and specific antimicrobial resistance rates. The current findings pointed out some directions to pursue in controlling the prevalence of certain resistant bacterial strains in children.

Why Do We Pursue Ed.D.?: A Qualitative Analysis on the Motivation of Chinese Candidates.

This study aims to explore what motivates Chinese mid-career educational practitioners to pursue Ed. D. A university in South China was selected as a case university, and 18 Ed.D. candidates were recruited to participate in semi-structured interviews. Grounded theory analysis was conducted on the transcripts of the interviewees' information. The findings uncovered four motivational patterns (pre-intrinsic, pre-extrinsic, post-intrinsic, and post-extrinsic) of Ed.D. candidates in China that mutually influence and reinforce one another. A theoretical model was thus constructed in which extrinsic factors moderate intrinsic factors, prepositional factors stimulate post-positional factors, with pre-intrinsic factors act as incentives, pre-extrinsic factors act as preconditions, and post-intrinsic factors and post-extrinsic factors act as internal and external reinforcers, respectively. This study broadens critical understanding of Ed.D. students' motivation and offers several implications that should be of interest to Chinese Ed.D. candidates, educational researchers, universities, and government officials.

Molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae among children in China.

Klebsiella pneumoniae infection and antimicrobial resistance among children are major concerns. The occurrence of hypervirulent K. pneumoniae (hvKp) infections is gradually increasing worldwide, and disinfectant resistance is also being reported. Carbapenem- and disinfectant-resistant hvKp infection has made clinical treatment and nosocomial infection control among children increasingly challenging. In this study, whole-genome sequencing was conducted among 34 Carba NP-positive carbapenem-resistant K. pneumoniae (CRKP) strains, and the distribution of antibiotic resistance genes, virulence genes and disinfectant resistance genes was determined. Eleven distinct STs were identified, and most of them were ST11 (58.8%). Among the carbapenem resistance genes, KPC-2 was predominant (61.8%), followed by NDM-1 (26.5%) and IPM-4 (11.8%), and no other carbapenemase genes were found. Twelve virulence genes were investigated. All 34 CRKP strains carried the following virulence genes: rcsA/B, entA, fimA/H and mrkA/D. The gene iucB was present in only 3 (8.9%) CRKP strains. The positive detection rates of the iroN and ybtA genes were 94.1% and 64.7%, respectively. None of the strains was found to carry the rmpA and iroB genes. Two disinfectant resistance genes were investigated in this study. Twenty-one (61.8%) strains carried both the qacE and cepA disinfectant resistance genes, 13 (38.2%) CRKP strains carried only the cepA gene, and no strains with only the qacE gene was detected. The correlations among virulence, drug resistance and disinfectant tolerance showed that the virulence and disinfectant resistance genes were distinct among several types of carbapenemase-producing CRKP strains.

Facile preparation of sulfonated biochar for highly efficient removal of toxic Pb(II) and Cd(II) from wastewater.

Biochar is deemed as the ideal material for the effective removal of heavy metals in wastewater treatment. Herein, we developed a facile one-step solvothermal method for the preparation of sulfonated biochar (SBC) from Axonopus compressus under a low-temperature condition. FTIR and XPS analysis demonstrate that plenty of -OH, -COOH and -SO3H moieties are generated on the surface of SBC during the sulfonation process. Due to high electronegativity and strong complexation of these moieties, SBC can rapidly adsorb Pb(II) and Cd(II) with capacities of 191.07 and 85.76 mg/g respectively within 5 min. SBC can be reused for 5 cycles with a negligible loss of adsorption capacity. In addition, different biomass-based biochars are prepared under the identical experimental conditions, and they are successfully applied in the treatments of Pb(II) and Cd(II). The satisfying results indicate that one-step low-temperature sulfonation could be a universal method, and various types of biomass waste could be the abundant, effective, economical material source for the treatment of environmental heavy metal pollution in future.

Scaling-up Atomically Thin Coplanar Semiconductor-Metal Circuitry via Phase Engineered Chemical Assembly.

Two-dimensional (2D) layered semiconductors, with their ultimate atomic thickness, have shown promise to scale down transistors for modern integrated circuitry. However, the electrical contacts that connect these materials with external bulky metals are usually unsatisfactory, which limits the transistor performance. Recently, contacting 2D semiconductors using coplanar 2D conductors has shown promise in reducing the problematic high contact resistance. However, many of these methods are not ideal for scaled production. Here, we report on the large-scale, spatially controlled chemical assembly of the integrated 2H-MoTe2 field-effect transistors (FETs) with coplanar metallic 1T'-MoTe2 contacts via phase engineered approaches. We demonstrate that the heterophase FETs exhibit ohmic contact behavior with low contact resistance, resulting from the coplanar seamless contact between 2H and 1T'-MoTe2 confirmed by transmission electron microscopy characterizations. The average mobility of the heterophase FETs was measured to be as high as 23 cm2 V-1 s-1 (comparable with those of exfoliated single crystals), due to the large 2H-MoTe2 single-crystalline domain size (486 ± 187 µm). By developing a patterned growth method, we realize the 1T'-MoTe2 gated heterophase FET array whose components of the channel, gate, and contacts are all 2D materials. Finally, we transfer the heterophase device array onto a flexible substrate and demonstrate the near-infrared photoresponse with high photoresponsivity (∼1.02 A/W). Our study provides a basis for the large-scale application of phase-engineered coplanar MoTe2 semiconductor-metal structure in advanced electronics and optoelectronics.

Millimeter-Scale Single-Crystalline Semiconducting MoTe2 via Solid-to-Solid Phase Transformation.

Among the Mo- and W-based two-dimensional (2D) transition metal dichalcogenides, MoTe2 is particularly interesting for phase-engineering applications, because it has the smallest free energy difference between the semiconducting 2H phase and metallic 1T' phase. In this work, we reveal that, under the proper circumstance, Mo and Te atoms can rearrange themselves to transform from a polycrystalline 1T' phase into a single-crystalline 2H phase in a large scale. We manifest the mechanisms of the solid-to-solid transformation by conducting density functional theory calculations, transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy. The phase transformation is well described by the time-temperature-transformation diagram. By optimizing the kinetic rates of nucleation and crystal growth, we have synthesized a single-crystalline 2H-MoTe2 domain with a diameter of 2.34 mm, a centimeter-scale 2H-MoTe2 thin film with a domain size up to several hundred micrometers, and a seamless 1T'-2H MoTe2 coplanar homojunction. The 1T'-2H MoTe2 homojunction provides an elegant solution for ohmic contact of 2D semiconductors. The controlled solid-to-solid phase transformation in 2D limit provides a new route to realize wafer-scale single-crystalline 2D semiconductor and coplanar heterostructure for 2D circuitry.

High-intensity focused ultrasound combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: long-term follow-up and clinical analysis.

OBJECTIVE: High-intensity focused ultrasound (HIFU) combined with transarterial chemoembolization (TACE) has been used to treat unresectable HCC, but its long-term effects and major prognostic factors remain to be determined. The purpose of this study was to assess its long-term effects and find major prognostic factors to help us select eligible patients in the future. METHODS: 73 patients with unresectable HCC received follow-up after HIFU+TACE. The variables of sex, age, AFP level, liver function, tumor location, tumor number, tumor size, TNM staging (5th edition), TNM staging (6th edition), portal vein invasion, ultrasonic pathway of HIFU, TACE session and ablation response were evaluated by univariate analysis. Those variables with significant difference were assessed by multivariate analysis. RESULTS: The mean follow-up time was 11.7±11.1 months (range, 1-60 months). The median survival time and overall survival rates of 1, 2, 3-year were 12 months, 49.1%, 18.8%, 8.4%, respectively. 45.2% patients achieved complete ablation. At the end of follow-up, 51 patients (69.9%) died from tumor progression (27 patients), liver function failure (18 patients), hemorrhage of upper digestive tract (3 patients) and infection (3 patients). 1 with liver abscess, 2 with serious skin burns and 2 with rib fracture were observed after HIFU. On univariate analysis, age (P=0.017), tumor size (P=0.000), tumor number (P=0.039), the 5th edition of TNM staging (P=0.023), portal vein invasion (P=0.02) and ablation response (P=0.000) had significant difference. On multivariate analysis, ablation response (P=0.001) and tumor size (P=0.013) were major prognostic factors. CONCLUSION: HIFU combined with TACE is a safe method with a low rate of severe complications. As major prognostic factors, ablation response and tumor size may help us predict the survival and select eligible patients clinically.