Room-Temperature Synthesis of Covalently Bridged MOP@TpPa-CH3 Composite Photocatalysts for Artificial Photosynthesis.

The conversion of CO2 into useful chemicals via photocatalysts is a promising strategy for resolving the environmental problems caused by the addition of CO2. Herein, a series of composite photocatalysts MOP@TpPa-CH3 based on MOP-NH2 and TpPa-CH3 through covalent bridging have been prepared via a facile room-temperature evaporation method and employed for photocatalytic CO2 reduction. The photocatalytic performances of MOP@TpPa-CH3 are greater than those of TpPa-CH3 and MOP-NH2, where the CO generation rate of MOP@TpPa-CH3 under 10% CO2 still reaches 119.25 µmol g-1 h-1, which is 2.18 times higher than that under pure CO2 (54.74 µmol g-1 h-1). To investigate the structural factors affecting the photocatalytic activity, MOP@TBPa-CH3 without C═O groups is synthesized, and the photoreduction performance is also evaluated. The controlling experimental results demonstrate that the excellent photoreduction CO2 performance of MOP@TpPa-CH3 in a 10% CO2 atmosphere is due to the presence of C═O groups in TpPa-CH3. This work offers a new design and construction strategy for novel MOP@COF composites.

Super-enhancer omics in stem cell.

The hallmarks of stem cells, such as proliferation, self-renewal, development, differentiation, and regeneration, are critical to maintain stem cell identity which is sustained by genetic and epigenetic factors. Super-enhancers (SEs), which consist of clusters of active enhancers, play a central role in maintaining stemness hallmarks by specifically transcriptional model. The SE-navigated transcriptional complex, including SEs, non-coding RNAs, master transcriptional factors, Mediators and other co-activators, forms phase-separated condensates, which offers a toggle for directing diverse stem cell fate. With the burgeoning technologies of multiple-omics applied to examine different aspects of SE, we firstly raise the concept of "super-enhancer omics", inextricably linking to Pan-omics. In the review, we discuss the spatiotemporal organization and concepts of SEs, and describe links between SE-navigated transcriptional complex and stem cell features, such as stem cell identity, self-renewal, pluripotency, differentiation and development. We also elucidate the mechanism of stemness and oncogenic SEs modulating cancer stem cells via genomic and epigenetic alterations hijack in cancer stem cell. Additionally, we discuss the potential of targeting components of the SE complex using small molecule compounds, genome editing, and antisense oligonucleotides to treat SE-associated organ dysfunction and diseases, including cancer. This review also provides insights into the future of stem cell research through the paradigm of SEs.

[Discussion on reference sample research of traditional Chinese medicine compound preparations developed from catalogued ancient classical prescriptions].

The concept of reference sample was put forward in the Guidance on CMC of Traditional Chinese Medicine Compound Preparations Developed from Catalogued Ancient Classical Prescriptions(Interim). The research on reference sample is a key link in the research and development of traditional Chinese medicine(TCM) compound prescriptions from catalogued ancient classical prescriptions(known as Category 3.1 TCM). This paper discusses the content of research on reference sample by analyzing the characteristics of Category 3.1 TCM and the purpose of research on reference sample. Furthermore, suggestions on the research of reference sample are proposed according to the development and evaluation practice of Category 3.1 TCM and research achievements of TCM regulatory science, aiming to provide reference for colleagues in this industry.

Curcumin inhibits the proliferation and migration of osteosarcoma by regulating the expression of super-enhancer-associated genes. / å§œé»„ç´ é€šè¿‡è°ƒæŽ§è¶ çº§å¢žå¼ºå­ç›¸å ³åŸºå› æŠ‘åˆ¶éª¨è‚‰ç˜¤çš„å¢žæ®–å’Œè¿ç§».

OBJECTIVES: Super-enhancer-associated genes may be closely related to the progression of osteosarcoma, curcumin exhibits a certain inhibitory effect on tumors such as osteosarcoma. This study aims to investigate the effects of curcumin on osteosarcoma in vitro and in vivo, and to determine whether curcumin can inhibit the progression of osteosarcoma by suppressing the expression of super-enhancer-associated genes LIM and senescent cell antigen-like-containing domain 1 (LIMS1), secreted protein acidic and rich in cysteine (SPARC), and sterile alpha motif domain containing 4A (SAMD4A). METHODS: Human osteosarcoma cell lines (MG63 cells or U2OS cells) were treated with 5 to 50 µmol/L curcumin for 24, 48, and 72 hours, followed by the methyl thiazolyl tetrazolium (MTT) assay to detect cell viability. Cells were incubated with dimethyl sulfoxide (DMSO) or curcumin (2.5, 5.0 µmol/L) for 7 days, and a colony formation assay was used to measure in vitro cell proliferation. After treatment with DMSO or curcumin (10, 15 µmol/L), a scratch healing assay and a transwell migration assay were performed to evaluate cell migration ability. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) and Western blotting were used to detect mRNA and protein expression levels of LIMS1, SPARC, and SAMD4A in the cells. An osteosarcoma-bearing nude mouse model was established, and curcumin was administered via gavage for 14 days to assess the impact of curcumin on tumor volume and weight in vivo. Real-time RT-PCR was used to measure mRNA expression levels of LIMS1, SPARC, and SAMD4A in the cancer and adjacent tissues from 12 osteosarcoma patients. RESULTS: After treating cells with different concentrations of curcumin for 24, 48, and 72 hours, cell viability were all significantly decreased. Compared with the DMSO group, the colony formation rates in the 2.5 µmol/L and 5.0 µmol/L curcumin groups significantly declined (both P<0.01). The scratch healing assay showed that, compared with the DMSO group, the migration rates of cells in the 10 µmol/L and 15 µmol/L curcumin groups were significantly reduced. The exception was the 10 µmol/L curcumin group at 24 h, where the migration rate of U2OS cells did not show a statistically significant difference (P>0.05), while all other differences were statistically significant (P<0.01 or P<0.001). The transwell migration assay results showed that the number of migrating cells in the 10 µmol/L and 15 µmol/L curcumin groups was significantly lower than that in the DMSO group (both P<0.001). In the in vivo tumor-bearing mouse experiment, the curcumin group showed a reduction in tumor mass (P<0.01) and a significant reduction in tumor volume (P<0.001) compared with the control group. Compared with the DMSO group, the mRNA expression levels of LIMS1, SPARC, and SAMD4A in the 10 µmol/L and 15 µmol/L curcumin groups were significantly down-regulated (all P<0.05). Additionally, the protein expression level of LIMS1 in U2OS cells in the 10 µmol/L curcumin group was significantly lower than that in the DMSO group (P<0.05). Compared with adjacent tissues, the mRNA expression level of SPARC in osteosarcoma tissues was significantly increased (P<0.001), while the mRNA expression levels of LIMS1 and SAMD4A did not show statistically significant differences (both P>0.05). CONCLUSIONS: Curcumin inhibits the proliferation and migration of osteosarcoma both in vitro and in vivo, which may be associated with the inactivation of super-enhancer-associated gene LIMS1.

TBN as Organic Redox Cocatalyst for Oxidative Tiffeneau-Demjanov-Type Rearrangement Using O2 as Sole Oxidant.

The Tiffeneau-Demjanov-type rearrangement is a ring-expansion reaction involving the cationic rearrangement of cyclic alcohols. The carbocation intermediates can be generated in situ via various means, including Wacker oxidation. In near recent reports on the reinvestiagtions by Wahl et al. (Sietmann, J.; Tenberge, M.; Wahl, J. M. Wacker Oxidation of Methylenecyclobutanes: Scope and Selectivity in an Unusual Setting. Angew. Chem., Int. Ed. 2023, 62, e202215381) and Zhu et al. (Feng, Q.; Wang, Q.; Zhu, J.-P. Oxidative Rearrangement of 1,1-Disubstituted Alkenes to Ketones. Science 2023, 379, 1363-1368), stoichiometric oxidants were involved. In this work, we report the Tiffeneau-Demjanov-type rearrangement can be smoothly promoted by the Pd-TBN cocatalyzed aerobic Wacker oxidation using molecular oxygen as the sole oxidant. tert-Butanol is essential for achieving high yields. Since the first report by Grigg et al. in 1977 (Boontanonda, P.; Grigg, R. J. Palladium (II)-Catalysed Ring Expansion of Methylenecyclobutanes and Related Systems. J. Chem. Soc. Chem. Commun. 1977, 17, 583-584), the five-decade journey of Pd-catalyzed Tiffeneau-Demjanov-type rearrangement returns to the aerobic again.

Synthesis Enabled by E-to-Z Isomerization Using CBZ6 as Energy Transfer Photocatalyst.

The reactions of Z-isomers and E-isomers usually are different in consideration of the regioselectivity of chemoselectivity. The syntheses of Z-isomers are not feasible in many cases. The energy transfer (EnT) E/Z-photoisomerization might yield the Z-isomers. In this work, CBZ6 was proven to be an EnT photocatalyst for the E → Z-isomerization of C-C or C-N double bonds. The transformations of in situ generated Z-isomers of oximes and stilbenes consequently afforded the desired reversed Beckmann rearrangement products and phenanthrenes, respectively.

Efficacy of omadacycline in the treatment of Legionella pneumonia: a case report.

Legionella, one of the main pathogens that causes community-acquired pneumonia, can lead to Legionella pneumonia, a condition characterized predominantly by severe pneumonia. This disease, caused by the bacterium Legionella pneumophila, can quickly progress to critical pneumonia and is often associated with damage to multiple organs. As a result, it requires close attention in terms of clinical diagnosis and treatment. Omadacycline, a new type of tetracycline derivative belonging to the aminomethylcycline class of antibiotics, is a semi-synthetic compound derived from minocycline. Its key structural feature, the aminomethyl modification, allows omadacycline to overcome bacterial resistance and broadens its range of effectiveness against bacteria. Clinical studies have demonstrated that omadacycline is not metabolized in the body, and patients with hepatic and renal dysfunction do not need to adjust their dosage. This paper reports a case of successful treatment of Legionella pneumonia with omadacycline in a patient who initially did not respond to empirical treatment with moxifloxacin. The patient also experienced electrolyte disturbance, as well as dysfunction in the liver and kidneys, delirium, and other related psychiatric symptoms.

Ceftazidime/avibactam versus polymyxin B in carbapenem-resistant Klebsiella pneumoniae infections: a propensity score-matched multicenter real-world study.

OBJECTIVES: In this retrospective observational multicenter study, we aimed to assess efficacy and mortality between ceftazidime/avibactam (CAZ/AVI) or polymyxin B (PMB)-based regimens for the treatment of Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections, as well as identify potential risk factors. METHODS: A total of 276 CRKP-infected patients were enrolled in our study. Binary logistic and Cox regression analysis with a propensity score-matched (PSM) model were performed to identify risk factors for efficacy and mortality. RESULTS: The patient cohort was divided into PMB-based regimen group (n = 98, 35.5%) and CAZ/AVI-based regimen group (n = 178, 64.5%). Compared to the PMB group, the CAZ/AVI group exhibited significantly higher rates of clinical efficacy (71.3% vs. 56.1%; p = 0.011), microbiological clearance (74.7% vs. 41.4%; p < 0.001), and a lower incidence of acute kidney injury (AKI) (13.5% vs. 33.7%; p < 0.001). Binary logistic regression revealed that the treatment duration independently influenced both clinical efficacy and microbiological clearance. Vasoactive drugs, sepsis/septic shock, APACHE II score, and treatment duration were identified as risk factors associated with 30-day all-cause mortality. The CAZ/AVI-based regimen was an independent factor for good clinical efficacy, microbiological clearance, and lower AKI incidence. CONCLUSIONS: For patients with CRKP infection, the CAZ/AVI-based regimen was superior to the PMB-based regimen.

Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy.

Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed T test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using "H2O" autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance.

The relationship between serum coagulation parameters and the recurrence of chronic subdural hematoma.

The aim is to investigate the relationship between serum coagulation parameters (PT, APTT, D-D and FDP) before hospitalization and recurrence of chronic subdural hematoma (CSDH). 236 patients with CSDH who were diagnosed for the first time and had complete medical records were followed up for at least 90 days. Fifty patients (21.2%) had relapsed. Univariate analysis was conducted including general data, imaging data and test results. Serum coagulation parameters (PT, APTT, D-D and FDP) were detected for all CSDH patients. The study identified several factors that exhibited a significant correlation with chronic subdural hematoma (CSDH) recurrence. These factors included advanced age (p = 0.01), hypertension (p = 0.04), liver disease (p = 0.01), anticoagulant drug use (p = 0.01), antiplatelet drug use (p = 0.02), bilateral hematoma (p = 0.02), and single-layer hematoma (p = 0.01). In addition, the presence of fibrin/fibrinogen degradation products (FDP) exceeding 5 mg/L demonstrated a significant relationship with CSDH recurrence (P < 0.05). Notably, the combined assessment of D-dimer (D-D) and FDP exhibited a significant difference, particularly regarding recurrence within 30 days after surgery (P < 0.05). The simultaneous elevation of serum FDP and D-D levels upon admission represents a potentially novel predictor for CSDH recurrence. This finding is particularly relevant for patients who experience recurrence within 30 days following surgical intervention. Older individuals with CSDH who undergo trepanation and drainage should be closely monitored due to their relatively higher recurrence rate.

Young patient with a giant gastric bronchogenic cyst: A case report and review of literature.

BACKGROUND: Gastric bronchogenic cysts (BCs) are extremely rare cystic masses caused by abnormal development of the respiratory system during the embryonic period. Gastric bronchial cysts are rare lesions that were first reported in 1956; as of 2023, only 33 cases are available in the PubMed online database. BCs usually have no clinical symptoms in the early stage, and imaging findings also lack specificity. Therefore, they are difficult to diagnose before histopathological examination. CASE SUMMARY: A 34-year-old woman with respiratory distress presented at our hospital. Endoscopic ultrasound revealed an anechoic mass between the spleen, left kidney and gastric fundus, with hyperechogenic and soft elastography textures and with a size of approximately 6.5 cm × 4.0 cm. Furthermore, a computed tomography scan demonstrated high density between the posterior stomach and the spleen and the left kidney, with uniform internal density and a small amount of calcification. The maximum cross section was approximately 10.1 cm × 6.1 cm, and the possibility of a cyst was high. Because the imaging findings did not suggest a malignancy and because the patient required complete resection, she underwent laparotomy surgery. Intraoperatively, this cystic lesion was found to be located in the posterior wall of the large curvature of the fundus and was approximately 8 cm × 6 cm in size. Finally, the pathologists verified that the cyst in the fundus was a gastric BC. The patient recovered well, her symptoms of chest tightness disappeared, and the abdominal drain was removed on postoperative day 6, after which she was discharged on day 7 for 6 months of follow-up. She had no tumor recurrence or postoperative complications during the follow-up. CONCLUSION: This is a valuable report as it describes an extremely rare case of gastric BC. Moreover, this was a very young patient with a large BC in the stomach.

The Burgeoning Significance of Liquid-Liquid Phase Separation in the Pathogenesis and Therapeutics of Cancers.

Liquid-liquid phase separation (LLPS) is a physiological phenomenon that parallels the mixing of oil and water, giving rise to compartments with diverse physical properties. Biomolecular condensates, arising from LLPS, serve as critical regulators of gene expression and control, with a particular significance in the context of malignant tumors. Recent investigations have unveiled the intimate connection between LLPS and cancer, a nexus that profoundly impacts various facets of cancer progression, including DNA repair, transcriptional regulation, oncogene expression, and the formation of critical membraneless organelles within the cancer microenvironment. This review provides a comprehensive account of the evolution of LLPS from the molecular to the pathological level. We explore the mechanisms by through which biomolecular condensates govern diverse cellular physiological processes, encompassing gene expression, transcriptional control, signal transduction, and responses to environmental stressors. Furthermore, we concentrate on potential therapeutic targets and the development of small-molecule inhibitors associated with LLPS in prevalent clinical malignancies. Understanding the role of LLPS and its interplay within the tumor milieu holds promise for enhancing cancer treatment strategies, particularly in overcoming drug resistance challenges. These insights offer innovative perspectives and support for advancing cancer therapy.

[Proportion and Clinical Significance of γδT17/Th17/Tc17 Cells in Peripheral Blood of Uygur Patients with Chronic Lymphoblastic Leukemia].

OBJECTIVE: To explore the distribution of γδT17/Th17/Tc17 cells in the peripheral blood of Uygur patients with chronic lymphoblastic leukemia (CLL) and clinical significance. METHODS: ELISA method was used to detect the levels of IL-17, IL-23, IL-6, and IFN-γ in the peripheral blood serum of 53 newly diagnosed Uygur patients with CLL and 30 healthy controls. Flow cytometry was used to determine the proportion of γδT/γδT17/Th17/Tc17 cells in the peripheral blood of Uygur CLL patients and controls, and the changes of the abover indexes in CLL Binet staging were observed. RESULTS: Compared with the control group, the proportion of γδT cells, γδT17 cells, and Th17 cells in the peripheral blood of Uygur CLL patients increased significantly （P <0.05）. γδT17 cell proportion in total lymphocytes was significantly higher than Th17 and Tc17 cell proportions（P <0.05）, and proportions of γδT, γδT17 cells increased gradually as the disease progressed. The levels of cytokines IL-17, IL-23, and IL-6 in peripheral blood of Uygur patients with CLL were significantly higher than those in the control group（P <0.05）, while the level of cytokine IFN-γ was significantly lower（P <0.05）. The level of IL-17 in peripheral blood decreased gradually as the disease progressed（P <0.05）. CONCLUSION: γδT and γδT17 are abnormally highly expressed in Uygur CLL , which are related to the stage of disease and participate in the occurrence and development of CLL.

An injectable collagen peptide-based hydrogel with desirable antibacterial, self-healing and wound-healing properties based on multiple-dynamic crosslinking.

Conventional collagen-based hydrogels as wound dressing materials are usually lack of antibacterial activity and easily broken when encountering external forces. In this work, we developed a collagen peptide-based hydrogel as a wound dressing, which was composed of adipic acid dihydrazide functionalized collagen peptide (Col-ADH), oxidized dextran (ODex), polyvinyl alcohol (PVA) and borax via multiple-dynamic reversible bonds (acylhydrazone, amine, borate ester and hydrogen bonds). The injectable hydrogel exhibited satisfactory self-healing ability, antibacterial activity, mechanical strength, as well as good biocompatibility and biodegradability. In vivo experiments demonstrated the rapid hemostasis, accelerated cell migration, and promoted wound healing capacities of the hydrogel. These results indicate that the multifunctional collagen peptide-based hydrogel has great potentials in the field of wound dressings.

Personalized application of antimicrobial drugs in pediatric patients with augmented renal clearance: a review of literature.

The effect of renal functional status on drug metabolism is a crucial consideration for clinicians when determining the appropriate dosage of medications to administer. In critically ill patients, there is often a significant increase in renal function, which leads to enhanced drug metabolism and potentially inadequate drug exposure. This phenomenon, known as augmented renal clearance (ARC), is commonly observed in pediatric critical care settings. The findings of the current study underscore the significant impact of ARC on the pharmacokinetics and pharmacodynamics of antimicrobial drugs in critically ill pediatric patients. Moreover, the study reveals a negative correlation between increased creatinine clearance and blood concentrations of antimicrobial drugs. The article provides a comprehensive review of ARC screening in pediatric patients, including its definition, risk factors, and clinical outcomes. Furthermore, it summarizes the dosages and dosing regimens of commonly used antibacterial and antiviral drugs for pediatric patients with ARC, and recommendations are made for dose and infusion considerations and the role of therapeutic drug monitoring. CONCLUSION:  ARC impacts antimicrobial drugs in pediatric patients. WHAT IS KNOWN: • ARC is inextricably linked to the failure of antimicrobial therapy, recurrence of infection, and subtherapeutic concentrations of drugs. WHAT IS NEW: • This study provides an updated overview of the influence of ARC on medication use and clinical outcomes in pediatric patients. • In this context, there are several recommendations for using antibiotics in pediatric patients with ARC: 1) increase the dose administered; 2) prolonged or continuous infusion administration; 3) use of TDM; and 4) use alternative drugs that do not undergo renal elimination.

Identification and Fungicide Screening of Fungal Species Associated with Walnut Anthracnose in Shaanxi and Liaoning Provinces, China.

Walnut is cultivated around the world for its precious woody nut and edible oil. Recently, walnut infected by Colletotrichum spp. resulted in a great yield and quality loss. In August and September 2014, walnut fruits with anthracnose were sampled from two commercial orchards in Shaanxi and Liaoning provinces, and five representative isolates were used in this study. To identify the pathogen properly, four genes per region (internal transcribed spacer, glyceraldehyde-3-phosphate dehydrogenase, actin, and chitin synthase) were sequenced and used in phylogenetic studies. Based on multilocus phylogenetic analysis, five isolates clustered with Colletotrichum fioriniae, including its ex-type, with 100% bootstrap support. The results of multilocus phylogenetic analyses, morphology, and pathogenicity confirmed that C. fioriniae was one of the walnut anthracnose pathogens in China. All 13 fungicides tested inhibited mycelial growth and spore germination. Flusilazole, fluazinam, prochloraz, and pyraclostrobin showed the strongest suppressive effects on the mycelial growth than the others, the average EC50 values ranged from 0.09 to 0.40 µg/ml, and there was not any significant difference (P < 0.05). Pyraclostrobin, thiram, and azoxystrobin were the most effective fungicides on spore germination (P < 0.05), and the EC50 values ranged from 0.01 to 0.44 µg/ml. Pyraclostrobin, azoxystrobin, fluazinam, flusilazole, mancozeb, thiram, and prochloraz exhibited a good control effect on walnut anthracnose caused by C. fioriniae, and preventive activities were greater than curative activities. Pyraclostrobin at 250 a.i. µg/ml and fluazinam at 500 a.i. µg/ml provided the highest preventive and curative efficacy, and the values ranged from 81.3 to 82.2% and from 72.9 to 73.6%, respectively. As a consequence, mancozeb and thiram could be used at the preinfection stage, and pyraclostrobin, azoxystrobin, flusilazole, fluazinam, and prochloraz could be used at the early stage for effective prevention and control of walnut anthracnose caused by C. fioriniae. The results will provide more significant instructions for controlling the disease effectively in northern China.