Reductive dechlorination of 2,4-dichlorophenol by using MWCNTs-Pd/Fe nanocomposites prepared in the presence of ultrasonic irradiation.

The research on developing a purification technology for 2,4-dichlorophenol (2,4-DCP) polluted water with high efficiency and the low energy consumption is crucial for achieving several Sustainable Development Goals (SDGs). In order to achieve these goals, MWCNTs-Pd/Fe nanocomposites were prepared by Fe nanoparticles modified with multi-walled carbon nanotubes (MWCNTs) and palladium (Pd) in the presence of ultrasonic irradiation. The MWCNTs-Pd/Fe nanocomposites were characterized by using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and X-Ray Diffraction (XRD), and others. Characterization results confirmed that the MWCNTs-Pd/Fe was successfully prepared, with the particle size of 80 nm and the specific surface area of 89.5 m2/g confirmed. We studied the reductive dechlorination of 2,4-Dichlorophenol (2,4-DCP) by MWCNTs-Pd/Fe nanocomposites under different conditions, and the optimized experimental results were found when the Pd loading was 0.4 %, the pH was 3, and the temperature was 30 °C. The phenol yield increased from 76.5 % (without ultrasonic irradiation) to 92.3 % (with ultrasonic irradiation) in 300 min and the 2,4-DCP removal rate reached 98.7 % under the optimal conditions. Therefore, ultrasonic irradiation enhanced the performance of MWCNTs-Pd/Fe nanocomposites for 2,4-DCP removal. We also established the degradation mechanism of chlorophenol by analyzing the intermediates, and proposed the degradation kinetics model. The degradation of 2,4-DCP followed the pseudo-first-order kinetics with the rate constant of 0.05988 min-1. Also, this study demonstrated the potential of using ultrasonic irradiation to improve the properties and recovery of MWCNTs-Pd/Fe nanocomposites, contributing to achievement of the Sustainable Development Goals (SDGs), including SDG-3, SDG-6.

Modulation of chronic obstructive pulmonary disease progression by antioxidant metabolites from Pediococcus pentosaceus: enhancing gut probiotics abundance and the tryptophan-melatonin pathway.

Chronic obstructive pulmonary disease (COPD), a condition primarily linked to oxidative stress, poses significant health burdens worldwide. Recent evidence has shed light on the association between the dysbiosis of gut microbiota and COPD, and their metabolites have emerged as potential modulators of disease progression through the intricate gut-lung axis. Here, we demonstrate the efficacy of oral administration of the probiotic Pediococcus pentosaceus SMM914 (SMM914) in delaying the progression of COPD by attenuating pulmonary oxidative stress. Specially, SMM914 induces a notable shift in the gut microbiota toward a community structure characterized by an augmented abundance of probiotics producing short-chain fatty acids and antioxidant metabolisms. Concurrently, SMM914 synthesizes L-tryptophanamide, 5-hydroxy-L-tryptophan, and 3-sulfino-L-alanine, thereby enhancing the tryptophan-melatonin pathway and elevating 6-hydroxymelatonin and hypotaurine in the lung environment. This modulation amplifies the secretion of endogenous anti-inflammatory factors, diminishes macrophage polarization toward the M1 phenotype, and ultimately mitigates the oxidative stress in mice with COPD. The demonstrated efficacy of the probiotic intervention, specifically with SMM914, not only highlights the modulation of intestine microbiota but also emphasizes the consequential impact on the intricate interplay between the gastrointestinal system and respiratory health.

An Underwater Source Localization Method Using Bearing Measurements.

Angle-of-arrival (AOA) measurements are often used in underwater acoustical localization. Different from the traditional AOA model based on azimuth and elevation measurements, the AOA model studied in this paper uses bearing measurements. It is also often used in the Ultra-Short Baseline system (USBL). However, traditional acoustical localization needs additional range information. If the range information is unavailable, the closed-form solution is difficult to obtain only with bearing measurements. Thus, a localization closed-form solution using only bearing measurements is explored in this article. A pseudo-linear measurement model between the source position and the bearing measurements is derived, and considering the nonlinear relationship of the parameters, a weighted least-squares optimization equation based on multiple constraints is established. Different from the traditional two-step least-squares method, the semidefinite programming (SDP) method is designed to obtain the initial solution, and then a bias compensation method is proposed to further minimize localization errors based on the SDP result. Numerical simulations show that the performance of the proposed method can achieve Cramer-Rao lower bound (CRLB) accuracy. The field test also proves that the proposed method can locate the source position without range measurements and obtain the highest positioning accuracy.

TRIM28-Mediated Excessive Oxidative Stress Induces Cellular Senescence in Granulosa Cells and Contributes to Premature Ovarian Insufficiency In Vitro and In Vivo.

Premature ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by the abnormal alteration of hormone levels such as FSH and E2. POI causes infertility, severe daily life disturbances, and long-term health risks. However, the underlying mechanism remains largely unknown. In this study, we found that POI is associated with the cellular senescence of ovarian granulosa cells, and TRIM28 mediates oxidative stress (OS)-induced cellular senescence in granulosa cells. Mechanistically, OS causes a decrease in TRIM28 protein levels in KGN cells. Subsequently, it triggers an increase in the levels of autophagy marker proteins ATG5 and LC3B-II, and the downregulation of P62. Abnormal autophagy induces an increase in the levels of cellular senescence markers γ-H2A.X, P16, and P21, provoking cellular senescence in vitro. The overexpression of ovarian TRIM28 through a microinjection of lentivirus attenuated autophagy, cellular senescence, and follicular atresia in the ovaries of POI mice and improved mouse fertility in vivo. Our study highlights the triggers for POI, where the reduction of TRIM28, which is regulated by reactive oxygen species, causes follicular atresia and POI via triggering autophagy and inducing granulosa cell senescence. Shedding light on TRIM28 may represent a potential intervention strategy for POI.

Protein-assisted synthesis of chitosan-coated minicells enhance dendritic cell recruitment for therapeutic immunomodulation within pulmonary tumors.

The efficacy of cancer therapies is significantly compromised by the immunosuppressive tumor milieu. Herein, we introduce a previously unidentified therapeutic strategy that harnesses the synergistic potential of chitosan-coated bacterial vesicles and a targeted chemotherapeutic agent to activate dendritic cells, thereby reshaping the immunosuppressive milieu for enhanced cancer therapy. Our study focuses on the protein-mediated modification of bacterium-derived minicells with chitosan molecules, facilitating the precise delivery of Doxorubicin to tumor sites guided by folate-mediated homing cues. These engineered minicells demonstrate remarkable specificity in targeting lung carcinomas, triggering immunogenic cell death and releasing tumor antigens and damage-associated molecular patterns, including calreticulin and high mobility group box 1. Additionally, the chitosan coating, coupled with bacterial DNA from the minicells, initiates the generation of reactive oxygen species and mitochondrial DNA release. These orchestrated events culminate in dendritic cell maturation via activation of the stimulator of interferon genes signaling pathway, resulting in the recruitment of CD4+ and CD8+ cytotoxic T cells and the secretion of interferon-ß, interferon-γ, and interleukin-12. Consequently, this integrated approach disrupts the immunosuppressive tumor microenvironment, impeding tumor progression. By leveraging bacterial vesicles as potent dendritic cell activators, our strategy presents a promising paradigm for synergistic cancer treatment, seamlessly integrating chemotherapy and immunotherapy.

Progestin and adipoQ receptor 7 (PAQR7) mediate the anti-apoptotic effect of P4 on human granulosa cells and its deficiency reduces ovarian function in female mice.

PURPOSE: PAQR7 plays a key role in cell apoptosis as a progesterone membrane receptor. The physiological mechanism of PAQR7 in ovarian function and its anti-apoptotic action in mammals remain poorly understood. METHODS: We first added 0.2 µM aminoglutethimide (AG), an inhibitor of endogenous progesterone (P4) secretion, and transfected siPAQR7 co-incubated with P4 in human KGN cells to identify granulosa cell apoptosis, respectively. Additionally, we used Paqr7 knockout (PAQR7 KO) mice to assess the role of PAQR7 in the ovary. RESULTS: The PAQR7 deficiency significantly increased apoptosis of KGN cells, and this significant difference disappeared following P4 supplementation. The Paqr7-/- female mice showed a prolonged estrous cycle, reduced follicular growth, increased the number of atresia follicles, and decreased the concentrations of E2 and AMH. The litters, litter sizes, and spontaneous ovulation in the Paqr7-/- mice were significantly decreased compared with the Paqr7+/+ mice. In addition, we also found low expression of PAQR7 in GCs from human follicular fluids of patients diagnosed with decreased ovarian reserve (DOR) and ovaries of mice with a DOR-like phenotype, respectively. CONCLUSIONS: The present study has identified that PAQR7 is involved in mouse ovarian function and fertilization potential. One possible mechanism is mediating the anti-apoptotic effect of P4 on GC apoptosis via the BCL-2/BAX/CASPASE-3 signaling pathway. The mechanism underlying the effect of PAQR7 on ovarian development and aging remains to be identified.

Towards a new PhD Curriculum for Digital Finance.

The rapidly evolving field of Digital Finance necessitates a new, interdisciplinary approach to doctoral training. This manuscript presents a comprehensive curriculum designed to equip early-stage researchers with the skills and knowledge required to navigate the complexities of modern finance. The curriculum is structured around four pillars: Training through Research and Mandatory Scientific Training, Advanced Scientific Training, Transferable Skills Training, and Training through Secondments. Together, these pillars provide a balanced mix of theoretical knowledge, practical experience, and soft skills. The program also emphasizes international collaboration through conferences and offers online courses for accessibility and sustainability. By addressing key challenges such as data quality, deployment of complex models, trust in AI-supported products, and labor shortages, the program aims to foster innovation and competitiveness in the European Finance industry. The curriculum's alignment with the European Digital Finance Package and integration with leading institutions ensures its relevance and potential for significant impact.

The Development and Evaluation of a Prediction Model for Kidney Transplant-Based Pneumocystis carinii Pneumonia Patients Based on Hematological Indicators.

BACKGROUND: This study aimed to develop a simple predictive model for early identification of the risk of adverse outcomes in kidney transplant-associated Pneumocystis carinii pneumonia (PCP) patients. METHODS: This study encompassed 103 patients diagnosed with PCP, who received treatment at our hospital between 2018 and 2023. Among these participants, 20 were categorized as suffering from severe PCP, and, regrettably, 13 among them succumbed. Through the application of machine learning techniques and multivariate logistic regression analysis, two pivotal variables were discerned and subsequently integrated into a nomogram. The efficacy of the model was assessed via receiver operating characteristic (ROC) curves and calibration curves. Additionally, decision curve analysis (DCA) and a clinical impact curve (CIC) were employed to evaluate the clinical utility of the model. The Kaplan-Meier (KM) survival curves were utilized to ascertain the model's aptitude for risk stratification. RESULTS: Hematological markers, namely Procalcitonin (PCT) and C-reactive protein (CRP)-to-albumin ratio (CAR), were identified through machine learning and multivariate logistic regression. These variables were subsequently utilized to formulate a predictive model, presented in the form of a nomogram. The ROC curve exhibited commendable predictive accuracy in both internal validation (AUC = 0.861) and external validation (AUC = 0.896). Within a specific threshold probability range, both DCA and CIC demonstrated notable performance. Moreover, the KM survival curve further substantiated the nomogram's efficacy in risk stratification. CONCLUSIONS: Based on hematological parameters, especially CAR and PCT, a simple nomogram was established to stratify prognostic risk in patients with renal transplant-related PCP.

Validation of the kidney donor profile index (KDPI) for deceased donor kidney transplants in China.

BACKGROUND: The kidney donor profile index (KDPI) evaluates kidney donor's age, height, weight, ethnicity, cause of death, high blood pressure, diabetes, exposure to hepatitis C and estimated glomerular filtration (eGFR). Kidneys with lower KDPI scores are expected to function longer that those with higher KPDI values. The applicability of KDPI score in Chinese kidney transplant donation has not yet been validated. This study evaluated the prognostic value of KDPI score in Chinese kidney transplant patients. METHODS: A retrospective analysis was conducted on 184 deceased donors and 353 corresponding kidney transplant patients at the Organ Transplantation Department of Renmin Hospital of Wuhan University between 2018 and 2021. The donors and recipients were stratified into four groups based on their KDPI score: KDPI 85-100, KDPI 60-84, KDPI 21-59, and KDPI 0-20. RESULTS: As expected, the KDPI 85-100 group was associated with a poor short-term renal function (both postoperative creatinine and eGFR with P > 0.05), a higher incidence of delayed graft function (DGF; 25.5% for KDPI 85-100 group vs. 10.2% for KDPI 60-84 group vs. 5.4% for KDPI 21-59 group vs. 0 for KDPI 0-20 group, all P > 0.05). Furthermore, the same groups showed worse 3-year patient survival rate: 86.3% for KDPI 85-100 group vs. 97.01% for KDPI 60-84 group vs. 97.83% for KDPI 21-59 group vs. 100% for KDPI 0-20 group, all P > 0.05); and renal survival rate: 82.6% for KDPI 85-100 group vs. 92.99% KDPI 60-84 group vs.97.83% for KDPI 21-59 group vs. 100% for KDPI 0-20 group, all P > 0.05). Our analysis showed that the KDPI score had a good predictive value for the survival of kidney transplants and patients in our center (area under the curve: 0.728 and 0.76, P > 0.05). CONCLUSION: We recommend that the KDPI scoring system can be employed as an effective tool to predict kidney transplantation outcomes in deceased donation in China.

Fourier-transform microwave spectroscopy of the ClSO radical.

Pure rotational transitions of the ClSO radical have been observed by Fourier-transform microwave spectroscopy. a-type and b-type transitions, for both 35Cl and 37Cl isotopologues, were detected, and the observed very complicated fine and hyperfine components were assigned well. The intensities of the observed spectra of the two isotopologues correspond to the ratio of the isotope abundances of 35Cl and 37Cl. A total of 21 molecular constants were determined precisely for both 35ClSO and 37ClSO, including the rotational constants, centrifugal distortion constants, electronic spin-rotation constants, nuclear spin-rotation constants, magnetic hyperfine constants, and quadrupole coupling constants of chlorine. The molecular constants show ClSO to have the 2A'' electronic ground state with an out-of-plane unpaired electron. The spin density of the chlorine atom is about 10.6%, which is similar to that of the fluorine atom for FSO, about 8%. Results of the ClSO radical are compared with those of other triatomic radicals with similar structures, the XSS, XSO, and XOO radicals with X = H, F, and Cl, leading to a conclusion that the ClSO radical is more like FSO, but fairly different from the FOO and ClOO radicals.

Related health burden with the improvement of air quality across China.

BACKGROUND: Substantial progress in air pollution control has brought considerable health benefits in China, but little is known about the spatio-temporal trends of economic burden from air pollution. This study aimed to explore their spatio-temporal features of disease burden from air pollution in China to provide policy recommendations for efficiently reducing the air pollution and related disease burden in an era of a growing economy. METHODS: Using the Global Burden of Disease method and willingness to pay method, we estimated fine particulate matter (PM2.5) and/or ozone (O3) related premature mortality and its economic burden across China, and explored their spatio-temporal trends between 2005 and 2017. RESULTS: In 2017, we estimated that the premature mortality and economic burden related to the two pollutants were RMB 0.94 million (68.49 per 100,000) and 1170.31 billion yuan (1.41% of the national gross domestic product [GDP]), respectively. From 2005 to 2017, the total premature mortality was decreasing with the air quality improvement, but the economic burden was increasing along with the economic growth. And the economic growth has contributed more to the growth of economic costs than the economic burden decrease brought by the air quality improvement. The premature mortality and economic burden from O3 in the total loss from the two pollutants was substantially lower than that of PM2.5, but it was rapidly growing. The O3-contribution was highest in the Yangtze River Delta region, the Fen-Wei Plain region, and some western regions. The proportion of economic burden from PM2.5 and O3 to GDP significantly declined from 2005 to 2017 and showed a decreasing trend pattern from northeast to southwest. CONCLUSION: The disease burden from O3 is lower than that of PM2.5, the O3-contribution has a significantly increasing trend with the growth of economy and O3 concentration.

The oligodontia phenotype in a X-linked hypohidrotic ectodermal dysplasia patient with a novel EVC2 variant.

Objectives: To analyse the pathogenic genes in a patient with hypohidrotic ectodermal dysplasia (HED) and explore the relationship between pathogenic genes and the oligodontia phenotype. Methods: Clinical data and peripheral blood were collected from a patient with HED. Pathogenic genes were analysed by whole-exon sequencing (WES) and verified by Singer sequencing. The secondary and tertiary structures of the variant proteins were predicted to analyse their toxicity. Results: The patient exhibited a severe oligodontia phenotype, wherein only two deciduous canines were left in the upper jaw. WES revealed a hemizygous EDA variant c.466C > T p.(Arg156Cys) and a novel heterozygous EVC2 variant c.1772T > C p.(Leu591Ser). Prediction of the secondary and tertiary structures of the EDA variant p.(Arg156Cys) and EVC2 variant p.(Leu591Ser) indicated impaired function of both molecules. Conclusion: The patient demonstrated a more severe oligodontia phenotype when compared with the other patients caused by the EDA variant c.466C > T. Since Evc2 is a positive regulator of the Sonic Hedgehog (Shh) signal pathway, we speculated that the EVC2 variant p.(Leu591Ser) may play a synergistic role in the oligodontia phenotype of HED, thereby exacerbating the oligodontia phenotype. Knowledge of oligodontia caused by multiple gene variants is of great significance for understanding individual differences in oligodontia phenotypes.

Application of a rapid and sensitive RPA-CRISPR/Cas12a assay for naked-eye detection of Haemophilus parasuis.

BACKGROUND: Haemophilus parasuis (H. parasuis) is a gram-negative bacterial pathogen that causes severe infections in swine, resulting in substantial economic losses. Currently, the majority of H. parasuis detection methods are impractical for on-site application due to their reliance on large instruments or complex procedures. Thus, there is an urgent need to develop a rapid, visually detectable, and highly sensitive detection method, especially under resource-limited environments and field conditions. RESULTS: In this study, we established a naked eye assay for highly sensitive detection by combining recombinase polymerase amplification (RPA) with CRISPR/Cas12a technology. Positive samples exhibited a clear red color visible to the naked eye, while negative samples appeared blue. We achieved a remarkable sensitivity, detecting H. parasuis down to a single copy, with no cross-reactivity with other bacteria. In a mouse model, our assay detected H. parasuis infection nearly 8 h earlier than traditional PCR. Compared to qPCR, our detection results were 100 % accurate. To enhance point-of-care applicability and mitigate the risk of aerosol contamination from uncapping, we consolidated RPA and CRISPR/Cas12a cleavage into a single-tube reaction system. This integrated approach was validated with 20 clinical lung samples, yielding results consistent with those obtained from qPCR. The entire procedure, from DNA extraction to detection, was completed in 35 min. SIGNIFICANCE: We present an RPA-CRISPR/Cas12a assay suitable for the early and resource-efficient diagnosis of H. parasuis infections. Its simplicity and visual detection are advantageous for field diagnostics, representing a substantial develpoment in the diagnosis of H. parasuis.

Compound heterozygous WNT10A missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia.

BACKGROUND: The aim of this study was to analyse the differences in the phenotypes of missing teeth between a pair of brothers with hypohidrotic ectodermal dysplasia (HED) and to investigate the underlying mechanism by comparing the mutated gene loci between the brothers with whole-exome sequencing. METHODS: The clinical data of the patients and their mother were collected, and genomic DNA was extracted from peripheral blood samples. By Whole-exome sequencing filtered for a minor allele frequency (MAF) ≤0.05 non-synonymous single-nucleotide variations and insertions/deletions variations in genes previously associated with tooth agenesis, and variations considered as potentially pathogenic were assessed by SIFT, Polyphen-2, CADD and ACMG. Sanger sequencing was performed to detect gene variations. The secondary and tertiary structures of the mutated proteins were predicted by PsiPred 4.0 and AlphaFold 2. RESULTS: Both brothers were clinically diagnosed with HED, but the younger brother had more teeth than the elder brother. An EDA variation (c.878 T > G) was identified in both brothers. Additionally, compound heterozygous variations of WNT10A (c.511C > T and c.637G > A) were identified in the elder brother. Digenic variations in EDA (c.878 T > G) and WNT10A (c.511C > T and c.637G > A) in the same patient have not been reported previously. The secondary structure of the variant WNT10A protein showed changes in the number and position of α-helices and ß-folds compared to the wild-type protein. The tertiary structure of the WNT10A variant and molecular simulation docking showed that the site and direction where WNT10A binds to FZD5 was changed. CONCLUSIONS: Compound heterozygous WNT10A missense variations may exacerbate the number of missing teeth in HED caused by EDA variation.

The miR-7/EGFR axis controls the epithelial cell immunomodulation and regeneration and orchestrates the pathology in inflammatory bowel disease.

INTRODUCTION: The epithelial immunomodulation and regeneration are intrinsic critical events against inflammatory bowel disease (IBD). MiR-7 is well documented as a promising regulator in the development of various diseases including inflammatory diseases. OBJECTIVES: This study aimed to assess the effect of miR-7 in intestinal epithelial cells (IECs) in IBD. METHODS: MiR-7def mice were given dextran sulfate sodium (DSS) to induce enteritis model. The infiltration of inflammatory cells was measured by FCM and immunofluorescence assay. 5'deletion assay and EMSA assays were performed to study the regulatory mechanism of miR-7 expression in IECs. The inflammatory signals and the targets of miR-7 were analyzed by RNA-seq and FISH assay. IECs were isolated from miR-7def, miR-7oe and WT mice to identify the immunomodulation and regeneration capacity. IEC-specific miR-7 silencing expression vector was designed and administered by the tail vein into murine DSS-induced enteritis model to evaluate the pathological lesions of IBD. RESULTS: We found miR-7 deficiency improved the pathological lesions of DSS-induced murine enteritis model, accompanied by elevated proliferation and enhanced transduction of NF-κB/AKT/ERK signals in colonic IECs, as well as decreased local infiltration of inflammatory cells. MiR-7 was dominantly upregulated in colonic IECs in colitis. Moreover, the transcription of pre-miR-7a-1, orchestrated by transcription factor C/EBPα, was a main resource of mature miR-7 in IECs. As for the mechanism, EGFR, a miR-7 target gene, was downregulated in colonic IECs in colitis model and Crohn's disease patients. Furthermore, miR-7 also controlled the proliferation and inflammatory-cytokine secretion of IECs in response to inflammatory-signals through EGFR/NF-κB/AKT/ERK pathway. Finally, IEC-specific miR-7 silencing promoted the proliferation and transduction of NF-κB pathway in IECs and alleviated the pathological damage of colitis. CONCLUSION: Our results present the unknown role of miR-7/EGFR axis in IEC immunomodulation and regeneration in IBD and might provide clues for the application of miRNA-based therapeutic strategies in colonic diseases.

Identification of benzothiazoles as novel PCSK9 inhibitors.

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a clinically validated target on the treatment of cardiovascular disease (CVD). PCSK9 can regulate the hepatocyte surface low density lipoprotein receptor (LDLR) level by binding to LDLR and leading to their degradation in the lysosome. The clinical use of two monoclonal antibodies (alirocumab and evolocumab, approved in 2015) and one small interfering RNA (inclisiran, approved in 2020) which can inhibit PCSK9 function proved that they are very effective in lowering low density lipoprotein cholesterol (LDL-C). However, the high treatment costs and parenteral administration of these drugs prohibited widespread use and reduced their long-term advantage. Comparatively, small molecule drugs have many incomparable advantages of macromolecules, such as lower treatment cost, more drug administration options, superior pharmacokinetic properties, less adverse immunogenic responses and better affordable production. In this paper, we identified a series of benzothiazoles small molecule PCSK9 inhibitors through extensive screening. The structure and activity relationship (SAR) was summarized to facilitate further optimization. Moreover, the primary mechanism of action of the most potent compound was also investigated.

Discovery of Kinetin in inhibiting colorectal cancer progression via enhancing PSMB1-mediated RAB34 degradation.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Understanding the underlying mechanism driving CRC progression and identifying potential therapeutic drug targets are of utmost urgency. We previously utilized LC-MS-based proteomic profiling to identify proteins associated with postoperative progression in stage II/III CRC. Here, we revealed that proteasome subunit beta type-1 (PSMB1) is an independent predictor for postoperative progression in stage II/III CRC. Mechanistically, PSMB1 binds directly to onco-protein RAB34 and promotes its proteasome-dependent degradation, potentially leading to the inactivation of the MEK/ERK signaling pathway and inhibition of CRC progression. To further identify potential anticancer drugs, we screened a library of 2509 FDA-approved drugs using computer-aided drug design (CADD) and identified Kinetin as a potentiating agent for PSMB1. Functional assays confirmed that Kinetin enhanced the interaction between PSMB1 and RAB34, hence facilitated the degradation of RAB34 protein and decreased the MEK/ERK phosphorylation. Kinetin suppresses CRC progression in patient-derived xenograft (PDX) and liver metastasis models. Conclusively, our study identifies PSMB1 as a potential biomarker and therapeutic target for CRC, and Kinetin as an anticancer drug by enhancing proteasome-dependent onco-protein degradation.

Fourier-transform microwave spectroscopy of the s-trans-3-propenalyl (CH2CHCO) and 3-propenolyl (CH2CHCO) radicals.

Pure rotational transitions of two conformers of the CH2CHCO radical have been observed by Fourier-transform microwave spectroscopy, where one conformer is called the s-trans-3-propenalyl radical and the other the 3-propenolyl radical. The observed two conformers have different electronic states. The former, the s-trans-3-propenalyl radical, has the 2A' electronic state and can be written as CH2CHCO, where the unpaired electron resides mainly on the terminal CO carbon. On the other hand, the latter, 3-propenolyl radical has the 2A'' electronic state and can be written as CH2CHCO. We were able to observe pure rotational transitions of the two conformers. Since both of the species have an unpaired electron, there exist spin-rotation interactions due to the unpaired electron and the magnetic hyperfine interactions due to the three coupling protons. The observed very complicated spectra, caused by these interactions, were assigned, leading to detailed molecular constants including the fine and hyperfine coupling constants for both of the species. The determined molecular constants support the electronic structures of the two conformers. There exists a controversy as to which of the two conformers is the lowest energy one. Our present observation led to the conclusion that s-trans-3-propenalyl is the lowest energy conformer.

Smart Surfaces with pH-Responsiveness Enhanced by Multiscale Hierarchical Structures Fabricated by Laser Direct Writing.

In contemporary applications, smart surfaces capable of altering their properties in response to external stimuli have garnered significant attention. Nonetheless, the efficient creation of smart surfaces exhibiting robust and rapid responsiveness and meticulous controllability on a large scale remains a challenge. This paper introduces an innovative approach to fabricate smart surfaces with strong pH-responsiveness, combining femtosecond laser direct writing (LDW) processing technology with stimulus-responsive polymer grafting. The proposed model involves the grafting of poly(2-diethylaminoethyl methacrylate) (PDEAEMA) onto rough and patterned Au/polystyrene (PS) bilayer surfaces through Au-SH bonding. The incorporation of LDW processing technology extends the choice of microstructures and roughness achievable on material surfaces, while PDEAEMA imparts pH responsiveness. Our findings revealed that the difference in contact angle between acidic and basic droplets on the rough PDEAEMA-g-Au surface (∼118°) greatly surpasses that on the flat PDEAEMA-g-Au surface (∼72°). Next, by leveraging the precision control over surface microstructures enabled by the LDW processing technique, this difference was further augmented to ∼127° on the optimized patterned PDEAEMA-g-Au surface. Further, we created two distinct combined smart surfaces with varying wettability profiles on which the hydrophilic-hydrophobic boundaries exhibit reliable asymmetric wettability for acidic and basic droplets. Additionally, we prepared a separator, realizing a better visual distinction between acid and base and collecting them separately. Given the effective abilities found in this study, we postulate that our smart surfaces hold substantial potential across diverse applications, encompassing microfluidic devices, intelligent sensors, and biomedicine.

Genotypic diversity and antifungal susceptibility of Cryptococcus neoformans species complex from China, including the diploid VNIII isolates from HIV-infected patients in Chongqing region.

Although previous studies on the genotypic diversity and antifungal susceptibility of the Cryptococcus neoformans species complex (CNSC) isolates from China revealed ST5 genotype isolates being dominant, the information about the CNSC isolates from Chinese HIV-infected patients is limited. In this study, 171 CNSC isolates from HIV-infected patients in the Chongqing region of Southwest China were genotyped using the International Society for Human and Animal Mycology-multilocus sequence typing consensus scheme, and their antifungal drug susceptibilities were determined following CLSI M27-A3 guidelines. Among 171 isolates, six sequence types (STs) were identified, including the dominant ST5 isolates, the newly reported ST15, and four diploid VNIII isolates (ST632/ST636). Moreover, a total of 1019 CNSC isolates with STs and HIV-status information were collected and analyzed from Mainland China in the present study. A minimum spanning analysis grouped these 1019 isolates into three main subgroups, which were dominated by the ST5 clonal complex (CC5), followed by the ST31 clonal complex (CC31) and ST93 clonal complex (CC93). The trend of resistance or decreasing susceptibility of clinical CNSC isolates to azole agents within HIV-infected patients from the Chongqing region is increasing, especially resistance to fluconazole.

In this paper, novel ST15 and four diploid VNIII isolates (ST632/ST636) were found in 171 CNSC isolates in Southwest China, including evidence for resistance to fluconazole. Moreover, we clustered the 1019 clinical CNSC isolates reported so far from Mainland China into three major subgroups.