Synergistic effects of ceftazidime/avibactam combined with meropenem in a murine model of infection with KPC-producing Klebsiella pneumoniae.

OBJECTIVES: The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. METHODS: To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose-response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of blaKPC. RESULTS: The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. CONCLUSIONS: Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp.

A sharp and selective fluorescence paper-based sensor based on inner filter effect for ratiometric detection of four Sudan dyes in food matrix.

The addition of Sudan dyes with carcinogenic effects to food threatens human health. Herein, a ratiometric fluorescence strip consisting of core-shell upconversion particles (NaYF4:Yb,Tm@NaYF4:Yb,Er), metal-organic frameworks and dual-template molecularly imprinted polymers was developed to selectively and sensitively detect four Sudan dyes based on inner filter effect (detection time only takes 8 min). The high adsorption capacity of metal-organic frameworks and the greater overlap between the emission of NaYF4:Yb,Tm@NaYF4:Yb,Er and the absorbance of four Sudan dyes enable the signal responses to be more sensitive. The limits of detection in chilli powder samples are as low as 29.87 ng/g, 37.55 ng/g, 47.89 ng/g and 51.02 ng/g, with satisfactory recovery (93.32-103.4%) and minor relative standard deviations (≤4.3%). This method broadens the idea for low-cost and portable detection of multiple illegal additives in complex substrates with high selectivity and sensitivity based on one kind of fluorescent strip.

Regulating luminescence thermal quenching based on the synergistic effect of energy transfer and energy gap modulation.

Thermal quenching is the core challenge that hinders the application of luminescent materials. Herein, a synergistic mechanism involving energy transfer and energy gap modulation is proposed based on the local crystal field regulation around sensitizers. The substitution of coordination cation V5+/P5+ weakens the crystal field strength of the sensitizer Bi3+, and the weakening of crystal field splitting causes an increase in the 3P1 energy level, thus increasing its energy gap. Compared with the YVO4:Bi3+,Eu3+ phosphor, the thermal stability of the YV0.25P0.75O4:Bi3+,Eu3+ phosphor is significantly improved, and the relative emission intensity of Eu3+ continuously increases with heating and reaches 1.24 times the original intensity at 523 K and does not show a decreasing trend in the studied temperature range. The anti-thermal quenching performance is mainly attributed to the increasing thermal quenching activation energy (ΔE) of the sensitizer by energy gap modulation, which enhances the energy transfer to compensate thermal quenching. Based on the thermal quenching characteristics of the materials, an optical thermometer is designed. The maximum relative sensitivity (Sr) and absolute sensitivity (Sa) are as high as 1.74% K-1 and 0.59 K-1, respectively, and the minimum temperature resolution reaches 0.288 K. The synergistic effect between energy gap modulation of the sensitizer and energy transfer enables the regulation of thermal quenching. Thus, this study provides a new strategy for exploiting high-performance luminescent materials.

Two Pathological Fractures in a Patient with Chronic Abnormalities in Serum Markers Following Two Liver Transplantations: A Case Report and Literature Review.

Bone disease is a common complication following liver transplantation, often overlooked in clinical practice. Clinical diagnosis of post-liver transplantation bone disease is challenging, and there have been few case report in the literature. This case report presents a patient who underwent two liver transplant surgeries, exhibited good daily activity, and did not display typical clinical symptoms such as fatigue, bone pain, or spinal deformities associated with prolonged sitting or standing. However, within the fifth year after the second liver transplant, the patient experienced two consecutive fractures. In March 2023, the patient underwent the first bone density test, which revealed osteoporosis. This case highlights the fact that severe fractures after liver transplantation may not necessarily be accompanied by typical symptoms of bone disease. Without timely examination and early prevention, serious consequences may arise. Therefore, this condition requires attention, proactive prevention, early detection, and timely treatment. Additionally, a retrospective analysis of the patient's previous laboratory data revealed persistent abnormalities in serum markers such as hypocalcemia and elevated alkaline phosphatase levels after liver transplantation, emphasizing the importance of monitoring these serum markers.

[Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity].

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 µm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 µL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 µmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.

Combined cytotoxicity of phthalate esters on HepG2 cells: A comprehensive analysis of transcriptomics and metabolomics.

Phthalate esters (PAEs), widely used as plasticizers, may pose a potential environmental and human hazard. The aim of this study was to compare the cytotoxicity of di(2-ethylhexyl) phthalates (DEHP) and dibutyl phthalate (DBP)) after their exposure to HepG2 cells alone or in combination. HepG2 cells treated with individual/combined DEHP and DBP at a dose of 10-2 M for 24 h were selected for metabolome and transcriptome analysis. The results demonstrated that exposure to the mixtures of DEHP and DBP caused enhanced or reduced toxic effects regarding 8 pathways with 1065 downregulated genes and 643 upregulated genes, in comparison with those of single chemicals. The combined toxicity of mixture revealed both synergistic and antagonistic interactions between DEHP and DBP. Besides, combined exposure to DEHP and DBP promoted TCA cycle, pyrimidine, and purine metabolism, while an antagonistic effect on fatty acid derangement should require further investigation. To summarize, our results suggest that DEHP exposed alone or combined with DBP caused a variety of metabolic disorders, and the type of combination effects varied among metabolic pathways.

Hetero-Polyionic Hydrogels Enable Dendrites-Free Aqueous Zn-I2 Batteries with Fast Kinetics.

Rechargeable aqueous Zn-I2 batteries (ZIB) are regarded as a promising energy storage candidate. However, soluble polyiodide shuttling and rampant Zn dendrite growth hamper its commercial implementation. Herein, a hetero-polyionic hydrogel is designed as the electrolyte for ZIBs. On the cathode side, iodophilic polycationic hydrogel (PCH) effectively alleviates the shuttle effect and facilitates the redox kinetics of iodine species. Meanwhile, polyanionic hydrogel (PAH) toward Zn metal anode uniformizes Zn2+ flux and prevents surface corrosion by electrostatic repulsion of polyiodides. Consequently, the Zn symmetric cells with PAH electrolyte demonstrate remarkable cycling stability over 3000 h at 1 mA cm-2 (1 mAh cm-2 ) and 800 h at 10 mA cm-2 (5 mAh cm-2 ). Moreover, the Zn-I2 full cells with PAH-PCH hetero-polyionic hydrogel electrolyte deliver a low-capacity decay of 0.008 ‰ per cycle during 18 000 cycles at 8 C. This work sheds light on hydrogel electrolytes design for long-life conversion-type aqueous batteries.

Enhanced Polysulfide Trapping and Conversion by Amorphous-Crystalline Heterostructured MnO2 Interlayers for Li-S Batteries.

The practical application of lithium-sulfur batteries (LSBs) is still hindered by several technical issues, including severe polysulfide shuttling and sluggish redox kinetics, which reduces the sulfur utilization and further results in low energy density. Herein, amorphous-crystalline heterostructured MnO2 (ACM) prepared through a simple calcination process was employed as the functional interlayer to play a double role as effective trapper and multifunctional electrocatalyst for LSBs. ACM not only combines the strong sulfur chemisorption of the amorphous MnO2 (AM) and fast Li+ transportation of the crystalline MnO2(CM) but also accelerates the interface charge transfer at the amorphous/crystalline interfaces. The LSBs with such unique interlayer exhibited an excellent rate performance of 1155.5 mAh·g-1 at 0.2 C and 692.9 mAh·g-1 at 3 C and a low decay rate of 0.071% per cycle over 500 cycles at 0.5 C. Even for a high sulfur loading of 5 mg·cm-2 at 0.1 C, a high capacity retention of 92.3% could also be achieved after 100 cycles. The concept of amorphous-crystalline heterostructures prepared by crystallization regulation might also be used for other electronic devices and catalyst designs.

A test strip constructed by molecular imprinting for ratiometric fluorescence with ultra-low limit of detection for selective monitoring of Sudan I in chili powder.

An up-conversion molecularly imprinted ratiometric fluorescent probe with a monodisperse nuclear-satellite structure and its test strip are designed which can avoid fluorescent background interference to detect Sudan I in chili powder highly selective and sensitive. The detection mechanism is based on the selective recognition of Sudan I by imprinted cavities on the surface of ratiometric fluorescent probe and the inner filter effect between Sudan I molecules and the emission of up-conversion materials (NaYF4:Yb,Tm). Under optimized experimental conditions, the response of fluorescent ratio signals (F475/F645) of this test strip show a good linear relationship in the range 0.02-50 µM Sudan I. The limits of detection and quantitation are as low as 6 nM and 20 nM, respectively. Sudan I is selectively detected in the presence of fivefold higher concentrations of interfering substances (imprinting factor up to 4.4). Detection of Sudan I in chili powder samples show ultra-low LOD (44.7 ng/g), satisfactory recoveries (94.99-105.5%) and low relative standard deviation (≤ 2.0%). This research offers a reliable strategy and promising scheme for highly selective and sensitive detection of illegal additives in complex food matrix via an up-conversion molecularly imprinted ratiometric fluorescent test strip.

Atomically Dispersed Fe-N4 and Ni-N4 Independent Sites Enable Bidirectional Sulfur Redox Electrocatalysis.

Single-atom catalysts (SACs) with high atom utilization and outstanding catalytic selectivity are useful for improving battery performance. Herein, atomically dispersed Ni-N4 and Fe-N4 dual sites coanchored on porous hollow carbon nanocages (Ni-Fe-NC) are fabricated and deployed as the sulfur host for Li-S battery. The hollow and conductive carbon matrix promotes electron transfer and also accommodates volume fluctuation during cycling. Notably, the high d band center of Fe in Fe-N4 site demonstrates strong polysulfide affinity, leading to an accelerated sulfur reduction reaction. Meanwhile, Li2S on the Ni-N4 site delivers a metallic property with high S 2p electron density of states around the Femi energy level, enabling a low sulfur evolution reaction barrier. The dual catalytic effect on Ni-Fe-NC endows sulfur cathode high energy density, prolonged lifespan, and low polarization.

Prevalence and risk factors of covert hepatic encephalopathy in cirrhotic patients: A multicenter study in China.

OBJECTIVE: We aimed to investigate the prevalence of covert hepatic encephalopathy (CHE) in cirrhotic patients in China and its risk factors. METHODS: A multicenter prospective observational study was conducted from January 2021 to March 2022 at 16 medical centers across China to investigate the risk factors of CHE and establish a prediction model for CHE episodes. RESULTS: A total of 528 patients were enrolled in the study. Based on both the psychometric hepatic encephalopathy score and Stroop test results, the prevalence of CHE was 50.4% (266/528), and the consistency between these two tests was 68.9%. Multivariate analysis showed that age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.022-1.063, P < 0.001), duration of education (OR 0.891, 95% CI 0.832-0.954, P = 0.001), comorbidities of cardiovascular diseases, hypertension, cerebral apoplexy or diabetes mellitus (OR 2.072, 95% CI 1.370-3.133, P < 0.001), Child-Pugh score (OR 1.142, 95% CI 1.029-1.465, P = 0.025), and blood urea nitrogen concentration (OR 1.126, 95% CI 1.038-1.221, P = 0.004) were associated with CHE episodes. According to the Chronic Liver Disease Questionnaire, CHE patients had lower scores for abdominal symptoms and systemic symptoms (P < 0.001), indicating a poor health-related quality of life. Based on a stepwise Cox regression hazard model, we established a nomogram for determining the probabilities of CHE episodes, and the area under the receiver operating characteristic curve was 0.733 (95% CI 0.679-0.788) and 0.713 (95% CI 0.628-0.797) in the training and validation cohorts. CONCLUSIONS: CHE is a common complication of cirrhosis in China. Large-scale studies with long-term follow-up are needed to determine the natural history of Chinese CHE patients.

The Age-Accompanied and Diet-Associated Remodeling of the Phospholipid, Amino Acid, and SCFA Metabolism of Healthy Centenarians from a Chinese Longevous Region: A Window into Exceptional Longevity.

As centenarians provide a paradigm of healthy aging, investigating the comprehensive metabolic profiles of healthy centenarians is of utmost importance for the pursuit of health and longevity. However, relevant reports, especially studies considering the dietary influence on metabolism, are still limited, mostly lacking the guidance of a model of healthy aging. Therefore, exploring the signatures of the integrative metabolic profiles of the healthy centenarians from a famous longevous region, Bama County, China, should be an effective way. The global metabolome in urine and the short-chain fatty acids (SCFAs) in the feces of 30 healthy centenarians and 31 elderly people aged 60−70 from the longevous region were analyzed by non-targeted metabolomics combined with metabolic target analysis. The results showed that the characteristic metabolites related to longevity were mostly summarized into phosphatidylserine, lyso-phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, bile acids, and amino acids (p < 0.05). Six metabolic pathways were found significant relevant to longevity. Furthermore, acetic acid, propionic acid, butyric acid, valeric acid, and total SCFA were significantly increased in the centenarian group (p < 0.05) and were also positively associated with the dietary fiber intake (p < 0.01). It was age-accompanied and diet-associated remodeling of phospholipid, amino acid, and SCFA metabolism that expressed the unique metabolic signatures related to exceptional longevity. This metabolic remodeling is suggestive of cognitive benefits, better antioxidant capacity, the attenuation of local inflammation, and health-span-promoting processes, which play a critical and positive role in shaping healthy aging.

Built-In Electric Field on the Mott-Schottky Heterointerface-Enabled Fast Kinetics Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries (LSBs) have been considered one of the most potential candidates to substitute traditional Li-ion batteries (LIBs), owing to their high theoretical energy density and low cost. Nevertheless, the shuttle effect and the sluggish redox kinetics of lithium polysulfides (LiPSs) have long been obstacles to realizing stable LSBs with high reversible capacity. In this study, we proposed a metal-semiconductor (Mo and MoO2) heterostructure with the hollow microsphere morphology as an effective Mott-Schottky electrocatalyst to boost sulfur electrochemistry. The hollow structure can physically inhibit the shuttling of LiPSs and accommodate the volume fluctuation during cycling. More importantly, the built-in electric field at the heterointerfacial sites can effectively accelerate the reduction of LiPSs and oxidation of Li2S, thereby reaching a high sulfur utilization. With the assistance of the Mo/MoO2 catalyst, the cell exhibited prominent rate capability and stable long-term cycling performance, showing a high capacity of 630 mA h·g-1 at 4 C and a low decay of 0.073% at 1 C after 500 cycles. Even with high areal sulfur loading of 10.0 mg·cm-2, high capacity and good cycle stability were achieved at 0.2 C under lean electrolyte conditions (E/S ratio of 6 µL·mg-1).

Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3/CREB axis.

The purpose of the present study is to define the role of sevoflurane (SEV) in hepatic ischemia-reperfusion (I/R) injury as well as its underlying mechanism. Initially, hepatic I/R animal models and I/R hepatocyte models were established in C57BL/6 mice and normal mouse hepatocytes (BNL CL.2) after SEV preconditioning, respectively, followed by detection of microRNA-124-3p (miR-124-3p), TRAF3, and CREB expression by RT-qPCR and Western blot analysis. In addition, miR-124-3p, TRAF3 and CREB expression in hepatocytes was altered to identify their roles in modulating the levels of glutathione transferase (GST), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and inflammation-related factors and hepatocyte apoptosis by ELISA and flow cytometry respectively. The effects of SEV on the miR-124-3p/TRAF3/CREB axis were also verified in vitro and in vivo. IP assay was performed to verify the effect of TRAF3 on CREB ubiquitination in BNL CL.2 cells, and the cycloheximide (CHX) intervention experiment to detect the stability of CREB protein. SEV augmented the miR-124-3p expression in I/R animal and cell models. Moreover, SEV was observed to suppress I/R-induced liver damage, GST, ALT, and AST levels, hepatocyte apoptosis and inflammation. Overexpression of miR-124-3p resulted in alleviation of hepatic I/R injury, which was countered by TRAF3 overexpression. miR-124-3p targeted TRAF3, while TRAF3 promoted CREB ubiquitination and reduced protein stability of CREB. SEV could impede I/R-induced liver damage, GST, ALT, and AST levels, hepatocyte apoptosis and inflammation via mediation of the miR-124-3p/TRAF3/CREB axis in vitro and in vivo. Collectively, SEV may upregulate miR-124-3p to inhibit TRAF3 expression, thereby reducing the ubiquitination and degradation of CREB, alleviating hepatic I/R injury.

Regulatory mechanisms of Beta-carotene and BCMO1 in adipose tissues: A gene enrichment-based bioinformatics analysis.

Beta-carotene (ß-carotene, BC) is one of the carotenoids most commonly consumed by humans. BCMO1 is expressed in various human tissues and is considered to be a key enzyme that converts BC into vitamin A. Studies indicated that BC-derived carotenoid signaling molecules affected the physiological functions of fat cells. In order to investigate the role and possible molecular mechanism of BC in mouse adipocytes, we conducted 4-group and 2-group difference analysis based on the data of GSE27271 chip in the Gene Expression Omnibus database. Genes differentially expressed in the inguinal white adipose tissue of mice were screened out and combined with the STRING database to construct protein-protein interaction (PPI) networks. Among them, Alb (albumin), Mug1 (murinoglobulin-1) and Uox (urate oxidase) genes were at relatively key positions and may affect the action of BC. Besides, Ppara (peroxisome proliferator-activated receptor alpha), Acly (ATP-citrate lyase) and Fabp5 (fatty acid-binding protein 5) genes constituted functional partners with many genes in the PPI network, and these genes may be Bcmo1 targeting molecules. Gene Ontology (GO) function and signaling pathways enrichment analysis were performed on the genes with protein interaction relationship in the PPI network. Fatty acid binding, cholesterol metabolic process, and regulation of fatty acid metabolic process were significantly enriched, and PPAR signaling pathway showed the most significant, indicating that BC and Bcmo1 might synergistically affect body metabolic functions such as fat metabolism. In general, BC and Bcmo1 may play a role in fat metabolism in mice, thereby affecting other functions or diseases.

Low-level viremia in nucleoside analog-treated chronic hepatitis B patients.

ABSTRACT: Low-level viremia (LLV) was defined as persistent or intermittent episodes of detectable hepatitis B virus (HBV) DNA (<2000 IU/mL, detection limit of 10 IU/mL) after 48 weeks of antiviral treatment. Effective antiviral therapies for chronic hepatitis B (CHB) patients, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), have been shown to inhibit the replication of HBV DNA and prevent liver-related complications. However, even with long-term antiviral therapy, there are still a number of patients with persistent or intermittent LLV. At present, the research on LLV to address whether adversely affect the clinical outcome is limited, and the follow-up treatment for these patients is open to question. At the same time, the mechanism of LLV is not clear. In this review, we summarize the incidence of LLV, the association between LLV and long-term outcomes, possible mechanisms, and management strategies in these patient populations.

Examination of the differences between sulforaphane and sulforaphene in colon cancer: A study based on next-generation sequencing.

Sulforaphane and sulforaphene are isothiocyanate compounds derived from cruciferous vegetables that have demonstrated antiproliferative properties against colon cancer. However, the underlying mechanism of action of these two compounds has yet to be elucidated. The aim of the present study was to examine the effects of sulforaphane and sulforaphene on colon cancer using next-generation sequencing (NGS). The SW480 colon cancer cell line was cultured with 25 µmol/l sulforaphane or sulforaphene. Total RNA was extracted from the cells following 48 h of incubation with these compounds, and NGS was performed. Pearson's correlation and principal component analyses were performed on the NGS data in order to determine sample homogeneity followed by hierarchical clustering, chromosomal location, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A total of 873 probes in the sulforaphene group were differentially expressed compared with the control group. Similarly, 959 probes in the sulforaphane group were differentially expressed compared with the control group. The differentially expressed genes were dispersed on the chromosomes, across 22 pairs of autosomes, as well as the X and Y chromosomes. GO and KEGG analyses demonstrated that both drugs affected the 'p53 signaling pathway', 'MAPK signaling pathway', 'FOXO signaling pathway' and 'estrogen signaling pathway', while 'Wnt signaling pathway' was enriched in the sulforaphane group, and 'ubiquitin mediated proteolysis' and 'estrogen signaling pathway' in the sulforaphene group. Thus, sulforaphane and sulforaphene exhibited similar biological activities on colon cancer cells. Sulforaphane and sulforaphene may be associated with Wnt and estrogen signaling, respectively.

Myeloid sarcoma of the colon as initial presentation in acute promyelocytic leukemia: A case report and review of the literature.

BACKGROUND: Myeloid sarcoma (MS) rarely occurs in acute promyelocytic leukemia (APL) at onset, but it can develop in relapse cases, especially after APL treated with all-trans retinoic acid (ATRA). Therefore little is known about the clinical features and suitable treatment for APL related MS due to the rarity of the disease, although this may be different from the treatment and prognosis of MS in the relapse stage. To our best knowledge, this is the second case report of APL initial presentation as colon MS. CASE SUMMARY: A 77-year-old woman complained of intermittent right lower abdominal pain, black stool, and difficult defecation for 2 mo. Physical examination showed diffuse tenderness during deep palpation and an anemic appearance. Laboratory findings showed positivity for fecal occult blood testing; white blood cell count: 3.84 × 109/L; hemoglobin: 105 g/L; platelet count: 174 × 109/L; and negativity for tumor markers. Abdominal enhanced computed tomography showed a space occupying lesion in the colon (1.9 cm). Fibrocolonoscopy revealed a polypoid and ulcerated mass measuring 2.5 cm. The tumor was removed. To our surprise, MS was confirmed by immunohistochemistry. PML/RARα fusion gene was detected in colon specimens by fluorescent in situ hybridization and real-time reverse transcription polymerase chain reaction, which was consistent with the bone marrow. She was diagnosed as having APL related MS. A smooth and unobstructed intestinal wall was found by fibrocolonoscopy, and continuous molecular remission was confirmed in both the bone marrow and colon after four courses of ATRA + arsenic trioxide (ATO). ATRA + ATO showed a favorable therapeutic response for both APL and MS. CONCLUSION: Early use of ATRA can benefit APL patients, regardless of whether MS is the first or recurrent manifestation.

Reducing tetracycline antibiotics residues in aqueous environments using Tet(X) degrading enzymes expressed in Pichia pastoris.

Tetracycline antibiotics (TCs) are massively produced and consumed in various industries resulting in large quantities of residuals in the environment. In this study, to achieve safe and efficient removal of residual TCs, a Pichia pastoris (P. pastoris) was gained to stably express glycosylated TCs degrading enzyme Tet(X) followed codon and expression parameter optimization of tet(X4). As expected, glycosylated Tet(X) still maintains efficient capacity of degrading TCs. The expressed Tet(X) maintained efficient TCs degrading ability over a pH range of 6.5 - 9.5 and temperature range of 17 - 47 °C. We tested this recombinant protein for its ability to degrade tetracycline in pond water and sewage models of tetracycline removal at starting levels of 10 mg/L substrate. 80.5 ± 3.8% and 26.2 ± 2.6% of tetracycline was degraded within 15 min in the presence of 0.2 µM Tet(X) and 50 µM NADPH, respectively. More importantly, the direct use of a Tet(X) degrading enzymes reduces the risk of gene transmission during degradation. Thus, the Tet(X) degrading enzyme expressed by P. pastoris is an effective and safe method for treating intractable TCs residues.

Dexmedetomidine Ameliorates Postoperative Cognitive Dysfunction via the MicroRNA-381-Mediated EGR1/p53 Axis.

Postoperative cognitive dysfunction (POCD; cognitive change associated with anesthesia and surgery) is one of the most serious long-term postoperative complications that occur in elderly patients. Dexmedetomidine (DEX) has been shown to be beneficial for improving outcomes of postoperative cognitive function. However, the exact mechanism underlying this role requires is yet to be found. The present study aims to determine the pathways involved in the protective effects of DEX against POCD in C57BL/6 J aged mice. DEX was administered after POCD modeling in C57BL/6 J aged mice. The cognitive function was evaluated after DEX treatment using novel object recognition, open field, and Y-maze tests. We also assessed its effects on neuron apoptosis and production of TNF-α and IL-1ß in mouse brain tissues as well as expression levels of DNA damage-related proteins p53, p21, and γH2AX. Interactions between early growth response 1 (EGR1) and p53, microRNA (miR)-381, and EGR1 were identified by ChIP and luciferase reporter assays, and gain- and loss-of-function experiments were performed to confirm the involvement of their interaction in POCD. DEX administration attenuated hippocampal neuron apoptosis, neuroinflammation, DNA damage, and cognitive impairment in aged mice. miR-381 targeted EGR1 and disrupted its interaction with p53, leading to a decline in hippocampal neuron apoptosis, DNA damage, neuroinflammation, and cognitive impairment. Furthermore, DEX administration resulted in the enhancement of miR-381 expression and the subsequent inhibition of EGR1/p53 to protect against cognitive impairment in aged mice. Overall, these results indicate that DEX may have a potential neuroprotective effect against POCD via the miR-381/EGR1/p53 signaling, shedding light on the mechanisms involved in neuroprotection in POCD.