Electrochemical Cross-Coupling between N-(4-Hydroxyphenyl)-sulfonamides and 2-Naphthols: Synthesis of 2,2'-Bis(arenol)s.

We herein present an electrochemical method for the dehydrogenative cross-coupling of N-(4-hydroxyphenyl)-sulfonamides and 2-naphthols. This transformation provides a direct and scalable approach to a wide range of C1-symmetric 2,2'-bis(arenol)s with moderate to high yields under mild conditions. Preliminary attempts with the asymmetric variant of this reaction were also performed with ≤55% ee for the synthesis of 2,2'-bis(arenol)s. Control experiments were conducted to propose a plausible mechanism for the reaction.

Temperature-Induced Interface Hybridization of WC Boosts NiCu Activity for Alkaline Hydrogen Oxidation Reaction.

The development of non-precious hydrogen oxidation reaction (HOR) catalysts is a major challenge for the commercialization of Pt-free fuel cells. Herein, a temperature-induced phase hybridization method is reported that greatly improves the catalytic performance of NiCu alloy for the HOR. The migration of W atoms hybridizes the interface of tungsten oxide (WOx) and tungsten carbide (WC) at the onset reduction temperature of WOx, leading to a greatly weakened H binding energy and an optimized OH binding energy, which endows NiCuW/WOx-WC@WC with favorable stability and CO resistance during HOR. The hybridization catalysts deliver a high mass activity of 29.37 mA mg-1 Ni and reach a peak power of 298 mW.cm-2 in H2-O2 anion exchange membrane fuel cells (AEMFCs).

Network meta-analysis of combination strategies in metastatic hormone-sensitive prostate cancer.

ABSTRACT: This study compared different doublet and triplet therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer (mHSPC). PubMed, EMBASE, and the Cochrane Library were comprehensively searched for eligible randomized controlled trials (RCTs) published from inception to October 2023. Interventions included abiraterone, apalutamide, enzalutamide, docetaxel, darolutamide, and androgen deprivation therapy (ADT), either as doublet or triplet therapies. The outcomes examined were overall survival (OS), progression-free survival (PFS), castration-resistant prostate cancer (CRPC)-free survival, time to symptomatic skeletal event (SSE), and toxicity. The surface under the cumulative ranking curve (SUCRA) was determined to identify the preferred treatments. Ten RCTs were included. The combination of darolutamide, docetaxel, and ADT had the highest SUCRA of 84.3 for OS, followed by combined abiraterone, docetaxel, and ADT (SUCRA = 71.6). The highest SUCRAs for PFS were observed for triplet therapies (abiraterone, docetaxel, and ADT [SUCRA = 74.9], followed by enzalutamide, docetaxel, and ADT [SUCRA = 74.3]) and other androgen receptor axis-targeted therapy-based doublet therapies (SUCRAs: 26.5-59.3). Darolutamide, docetaxel, and ADT had the highest SUCRAs, i.e., 80.8 and 84.0 regarding CRPC-free survival and time to SSE, respectively. Regarding Grade >3 adverse events (AEs), the SUCRAs of triplet therapies (SUCRAs: 14.8-31.5) were similar to that of docetaxel and ADT (SUCRA = 39.5). Three studies had a low risk of bias in all categories; the remaining studies had at least an unclear risk of bias in at least one category. Triplet therapy demonstrated potentially enhanced effectiveness than doublet therapy in mHSPC, with acceptable safety concerns. Darolutamide might be the optimal option for triplet therapy in combination with docetaxel and ADT.

Protein Arginine Methyltransferases in Pancreatic Ductal Adenocarcinoma: New Molecular Targets for Therapy.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant disease with a low 5-year overall survival rate. It is the third-leading cause of cancer-related deaths in the United States. The lack of robust therapeutics, absence of effective biomarkers for early detection, and aggressive nature of the tumor contribute to the high mortality rate of PDAC. Notably, the outcomes of recent immunotherapy and targeted therapy against PDAC remain unsatisfactory, indicating the need for novel therapeutic strategies. One of the newly described molecular features of PDAC is the altered expression of protein arginine methyltransferases (PRMTs). PRMTs are a group of enzymes known to methylate arginine residues in both histone and non-histone proteins, thereby mediating cellular homeostasis in biological systems. Some of the PRMT enzymes are known to be overexpressed in PDAC that promotes tumor progression and chemo-resistance via regulating gene transcription, cellular metabolic processes, RNA metabolism, and epithelial mesenchymal transition (EMT). Small-molecule inhibitors of PRMTs are currently under clinical trials and can potentially become a new generation of anti-cancer drugs. This review aims to provide an overview of the current understanding of PRMTs in PDAC, focusing on their pathological roles and their potential as new therapeutic targets.

A multicenter study of venetoclax-based treatment for patients with Richter transformation of chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) who develop Richter transformation (RT) have a poor prognosis when treated with chemoimmunotherapy regimens used for de novo diffuse large B-cell lymphoma. Venetoclax, a BCL2 inhibitor, has single agent efficacy in patients with RT and is potentially synergistic with chemoimmunotherapy. In this multicenter, retrospective study, we evaluated 62 patients with RT who received venetoclax-based treatment outside of a clinical trial, in combination with a Bruton tyrosine kinase inhibitor (BTKi; n=28), R-CHOP (n=13), or intensive chemoimmunotherapy other than R-CHOP (n=21). The best overall and complete response rates were 36%/25%, 54%/46%, and 52%/38%, respectively. The median progression-free and overall survival estimates for the same treatment groups were 4.9/14.3 months, 14.9 months/not reached, and 3.3/9 months, respectively. CLL with del(17p) was associated with a lower complete response rate in the total cohort (odds ratio [OR] 0.15; 95% confidence interval [CI] 0.04-0.6; p=0.01) and venetoclax-naïve subgroup (OR 0.13; 95%CI 0.02-0.66; p=0.01). TP53 mutated CLL was associated with a lower complete response rate (OR 0.15; 95%CI 0.03-0.74; p=0.02) and shorter progression-free survival (hazard ratio 3.1; 95%CI 1.21-7.95; p=0.02) only in venetoclax-naïve subgroup. No other clinical or baseline characteristics, including prior venetoclax treatment for CLL, showed statistically significant association with outcomes. Grade 3-4 neutropenia and thrombocytopenia events were most frequent with intensive chemoimmunotherapy + venetoclax; grade 3-4 infection rates were similar across treatment groups. In this difficult-to-treat RT patient population, venetoclax-based combination regimens achieved high response rates, with durable remission and survival observed in a subset of patients.

First Report of Powdery Mildew on Berchemia floribunda Caused by Erysiphe berchemiae in China.

The genus Berchemia (family Rhamnaceae), a group of climbing plants, is mainly distributed in Asia, Africa, and South America. Berchemia plants are widely used in traditional medicine in some Asian countries (Inoshiri et al. 1987). For example, in Japan, B. racemosa (synonym B. floribunda) is used for the treatment of gallstones, liver diseases, neuralgia, and stomach cramps, and in China, B. floribunda is used for the treatment of rheumatism and lumbago. In August 2022, typical powdery mildew symptoms were observed on wild B. floribunda plants in Huaxi District, Guiyang, Guizhou Province, China. The incidence was approximately 60% among 100 B. floribunda plants observed outdoors. White colonies almost entirely covered on both adaxial and abaxial surfaces of all leaves on symptomatic plants. Infected leaves appeared curled or chlorotic, infection occasionally leading to defoliation. To describe the pathogen morphologically, fungal samples were collected from two individual B. floribunda plants and microscopically characterized. In these samples, hyphae were flexuous to straight, branched, septate, 3-6 µm wide, with lobed hyphal appressoria. Conidiophores were erect, flexuous to straight, and 50-160 µm long (n = 30). Foot cells were subcylindrical to slightly curved-sinuous at the base, 20-40 µm long (n = 30), followed by 2-3 shorter cells. Conidia formed singly, occasionally 2-3 in a chain. Conidia were ellipsoid to ovoid, 20-42 × 12-18 µm (n = 50), without fibrosin bodies. Chasmothecia were not found. For molecular identification, the ribosomal DNA internal transcribed spacers (ITSs) of the two fungal samples were amplified and sequenced using the ITS1/ITS4 primer pair (White et al. 1990). The obtained 649-bp ITS sequences (GenBank accession nos. OR414364 and OR414365, respectively) shared 100% identity, and they showed 99.52% identity with the ITS sequence (GenBank accession no. LC009934) of Erysiphe berchemiae. Phylogenetic analysis grouped OR414364 and OR414365 in a clade with LC009934. Based on morphological and molecular characteristics, the powdery mildew fungus from B. floribunda was identified as E. berchemiae (Braun and Cook 2012). The voucher specimen (accession no. GZNU-BFEE/0820/2022) were deposited at the School of Life Sciences, Guizhou Normal University. Pathogenicity was assessed by gently pressing naturally diseased leaves of B. floribunda onto leaves of three healthy potted 1-year-old B. floribunda plants. Three non-inoculated healthy plants were used as controls. The plants were incubated in a greenhouse at 25 ± 2°C, 80% relative humidity. Similar powdery mildew symptoms were observed on the inoculated plants 9 days after inoculation, whereas the control plants remained symptomless. The reisolated fungus from inoculated leaves was morphologically identical to that observed on the original diseased leaves, and the ITS sequence of the reisolated fungus shared 100% identity with OR414364 and OR414365, fulfilling Koch's postulates. E. berchemiae has previously been described as a powdery mildew pathogen on B. yunnanensis (Chen et al. 1987) and B. kulingensis (Chen 1993) in China and B. racemosa (synonym B. floribunda) in Japan (Braun and Cook 2012; Takamatsu et al. 2015), but this is the first report of E. berchemiae causing disease of B. floribunda in China. This work suggests that E. berchemiae is an important pathogen of Berchemia plants, at least for some species in the genus Berchemia.

Vibration reduction of human body biodynamic response in sitting posture under vibration environment by seat backrest support.

Four-degree-of-freedom (4-DOF) human-chair coupling models are constructed to characterize the different contact modes between the head, chest back, waist back and backrest. The seat-to-head transfer ratio (STHT) is used as an evaluation metric for vibration reduction effectiveness. The simulated vibration reduction ratio of the model is close to the experimental results, which proves the validity of the model. The peak STHT is obviously reduced (P < 0.05, T-test) with seat-backrest support. The experiments show that supporting the head ( a 1 , P < 0.05, Wilcoxon matched-pairs signed ranks) has the best vibration reduction effect (21%), supporting the chest back ( a 2 , P < 0.05) has a reduced effect (11%), and supporting the waist back ( a 3 , P < 0.05) has the weakest effect (4%). When the upper torso is in full contact with the backrest, the peak STHT curve and resonance frequency are positively correlated with the contact stiffness of the seat surface and negatively correlated with the contact damping. In order to reduce the seat-to-head transfer ratio, the lowest STHT peak and lowest total energy judgments were proposed as the selection methods for the selection of the contact stiffness and damping of the backrest in two environments (periodic and non-periodic excitation), respectively.

Diagnostic and grading criteria for androgenetic alopecia using dermoscopy.

OBJECTIVES: To establish accurate and objective dermoscopic diagnostic criteria and grading standards for males and females with androgenetic alopecia (AGA). METHODS: Twenty patients each with AGA, diffuse alopecia areata, telogen effluvium, and healthy controls were enrolled in the current study. In addition, 60 patients with grades F1/V1, F2/V2, and F3/V3 AGA (20 cases each) were enrolled. The patients underwent dermoscopic examinations. The sensitivity and specificity of the diagnostic criteria were based on the 60 AGA and 60 non-AGA. In addition, 150 patients diagnosed with AGA clinically and by dermoscopy were enrolled to calculate the accuracy of the grading criteria. RESULTS: The diagnostic criteria included primary, secondary, and exclusion criteria. The grading criteria included three indices, which divided the severity of AGA into grades 1, 2, and 3. The sensitivity and specificity of the diagnostic criteria were 98.3% and 96.7% respectively. The accuracy of grade 1, 2, and 3 dermoscopic grading criteria were 96%, 92%, and 100% respectively, with a total accuracy of 96%. LIMITATIONS: To test the diagnostic and grading criteria, more patients need to be collected. CONCLUSIONS: The dermoscopic diagnostic and grading criteria are objective with good accuracy, which could provide a reasonable basis for the early diagnosis, grading treatment, and improved prognosis for AGA.

Tannic Acid-Modified Decellularized Tendon Scaffold with Antioxidant and Anti-Inflammatory Activities for Tendon Regeneration.

Tendon regeneration is greatly influenced by the oxidant and the inflammatory microenvironment. Persistent inflammation during the tendon repair can cause matrix degradation, tendon adhesion, and excessive accumulation of reactive oxygen species (ROS), while excessive ROS affect extracellular matrix remodeling and tendon integration. Herein, we used tannic acid (TA) to modify a decellularized tendon slice (DTS) to fabricate a functional scaffold (DTS-TA) with antioxidant and anti-inflammatory properties for tendon repair. The characterizations and cytocompatibility of the scaffolds were examined in vitro. The antioxidant and anti-inflammatory activities of the scaffold were evaluated in vitro and further studied in vivo using a subcutaneous implantation model. It was found that the modified DTS combined with TA via hydrogen bonds and covalent bonds, and the hydrophilicity, thermal stability, biodegradability, and mechanical characteristics of the scaffold were significantly improved. Afterward, the results demonstrated that DTS-TA could effectively reduce inflammation by increasing the M2/M1 macrophage ratio and interleukin-4 (IL-4) expression, decreasing the secretion of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), as well as scavenging excessive ROS in vitro and in vivo. In summary, DTS modified with TA provides a potential versatile scaffold for tendon regeneration.

A multiplex RPA-CRISPR/Cas12a-based POCT technique and its application in human papillomavirus (HPV) typing assay.

Persistent infection with high-risk human papillomavirus (HR-HPV) is the primary and initiating factor for cervical cancer. With over 200 identified HPV types, including 14 high-risk types that integrate into the host cervical epithelial cell DNA, early determination of HPV infection type is crucial for effective risk stratification and management. Presently, on-site immediate testing during the HPV screening stage, known as Point of Care Testing (POCT), remains immature, severely limiting the scope and scenarios of HPV screening. This study, guided by the genomic sequence patterns of HPV, established a multiplex recombinase polymerase amplification (RPA) technology based on the concept of "universal primers." This approach achieved the multiple amplification of RPA, coupled with the CRISPR/Cas12a system serving as a medium for signal amplification and conversion. The study successfully constructed a POCT combined detection system, denoted as H-MRC12a (HPV-Multiple RPA-CRISPR/Cas12a), and applied it to high-risk HPV typing detection. The system accomplished the typing detection of six high-risk HPV types (16, 18, 31, 33, 35, and 45) can be completed within 40 min, and the entire process, from sample loading to result interpretation, can be accomplished within 45 min, with a detection depth reaching 1 copy/µL for each high-risk type. Validation of the H-MRC12a detection system's reproducibility and specificity was further conducted through QPCR on 34 clinical samples. Additionally, this study explored and optimized the multiplex RPA amplification system and CRISPR system at the molecular mechanism level. Furthermore, the primer design strategy developed in this study offers the potential to enhance the throughput of H-MRC12a detection while ensuring sensitivity, providing a novel research avenue for high-throughput detection in Point-of-Care molecular pathogen studies.

Efficient production of R-2-(4-hydroxyphenoxy) propionic acid by Beauveria bassiana using biofilm-based two-stage fermentation.

In this work, a novel biofilm-based fermentation of Beauveria bassiana was employed to convert R-2- phenoxypropionic acid (R-PPA) to R-2-(4-hydroxyphenoxy) propionic acid (R-HPPA). The biofilm culture model of Beauveria bassiana produced a significantly higher R-HPPA titer than the traditional submerged fermentation method. Mannitol dosage, tryptone dosage, and initial pH were the factors that played a significant role in biofilm formation and R-HPPA synthesis. Under the optimal conditions, the maximum R-HPPA titer and productivity approached 22.2 g/L and 3.2 g/(L·d), respectively. A two-stage bioreactor combining agitation and static incubation was developed to further increase R-HPPA production. The process was optimized to achieve 100 % conversion of R-PPA, with a maximum R-HPPA titer of 50 g/L and productivity of 3.8 g/(L·d). This newly developed biofilm-based two-stage fermentation process provides a promising strategy for the industrial production of R-HPPA and related hydroxylated aromatic compounds.

Salmonella manipulates macrophage migration via SteC-mediated myosin light chain activation to penetrate the gut-vascular barrier.

The intestinal pathogen Salmonella enterica rapidly enters the bloodstream after the invasion of intestinal epithelial cells, but how Salmonella breaks through the gut-vascular barrier is largely unknown. Here, we report that Salmonella enters the bloodstream through intestinal CX3CR1+ macrophages during early infection. Mechanistically, Salmonella induces the migration/invasion properties of macrophages in a manner dependent on host cell actin and on the pathogen effector SteC. SteC recruits host myosin light chain protein Myl12a and phosphorylates its Ser19 and Thr20 residues. Myl12a phosphorylation results in actin rearrangement, and enhanced migration and invasion of macrophages. SteC is able to utilize a wide range of NTPs other than ATP to phosphorylate Myl12a. We further solved the crystal structure of SteC, which suggests an atypical dimerization-mediated catalytic mechanism. Finally, in vivo data show that SteC-mediated cytoskeleton manipulation is crucial for Salmonella breaching the gut vascular barrier and spreading to target organs.

Phosphorus release and realignment in anaerobic digestion of thermal hydrolysis pretreatment sludge - Masking effects from high ammonium.

Waste activated sludge (WAS) is a significant phosphorus (P) repository, and there is a growing interest in P recovery from WAS. Typically, the commercial technology for treating WAS involves thermal hydrolysis pretreatment (THP) coupled with anaerobic digestion (AD). However, there is ongoing debate regarding the transformation and distribution of P throughout this process. To address this, a long-term THP-AD process was operated in this study to comprehensively investigate P transformation and distribution. The results revealed that a substantial biodegradation of dissolved organic nitrogen (DON) raised the pH of the digestate to 8.3 during the AD process. This increased pH facilitated the dissolution of Al, leading to a reduction of 6.92 mg/L of NaOH-P. Simultaneously, sulfate reduction contributed to a decrease of 11.04 mg/L of Bipy-P in the solid. However, the reduction of Bipy-P and NaOH-P in the solid did not result in an improved P release to the supernatant. Conversely, a decrease of 23.60 mg/L P in the aqueous phase was observed after anaerobic digestion. The disappeared P was primarily precipitated with Mg and Ca, driven by the increased pH, and it contributed to the increase of HCl-P in the solid from 107.80 to 144.52 mg/L. These findings were further confirmed by results obtained from scanning electron microscopy (SEM), X-ray powder diffraction (XRD), and solid-state 31P nuclear magnetic resonance (NMR) spectroscopy. This study provides valuable insights into the mechanisms of P transformation during THP-AD process that is nearly opposite from conventional AD system.

Polarization sensitive optical side leakage radiometry for distributed characterization of anti-resonant hollow-core fibers.

A novel technique referred to as optical side leakage radiometry is proposed and experimentally demonstrated for non-destructive and distributed characterization of anti-resonant hollow-core optical fibers with high spatial resolution. Through in-depth analysis of the leakage light collection, we discover a unique polarization dependence, which is validated by our experiment. By leveraging this effect and employing Fourier filtering, this method enables accurate quantification of propagation attenuations for fundamental and higher order modes (with the uncertainty of <1 dB/km), identification of localized defects (with the resolution of ∼5 cm), and measurement of ultra-low spectral phase birefringence (at the level of 10-7) in two in-house-fabricated nested antiresonant nodeless hollow-core fibers. Such a fiber characterization approach, boasting unprecedently high accuracy and a potentially wide dynamic range, holds the potential to become an indispensable diagnosis tool for monitoring and assisting the manufacture of high-quality anti-resonant hollow-core fiber.

Association of the combination of obstructive sleep apnea risk and sleep duration with ideal cardiovascular health metrics in patients undergoing hemodialysis.

BACKGROUND: The purpose of this study was to explore the separate and combined associations of obstructive sleep apnea (OSA) risk and sleep duration with ideal cardiovascular health metrics in hemodialysis (HD) patients. METHODS: 470 HD participants (average: 59.48 ± 12.89 y, 281 men) were included in this study. Sleep duration was measured as self-reported average sleep time during the previous month. The OSA risk was assessed using the STOP-BANG questionnaire. Participants were divided into three groups based on the number of ideal cardiovascular health (CVH) metrics: 0-2,3-4, and 5-7. Ordinal logistic regression was conducted to model the associations of CVH metrics with sleep duration, OSA risk, and their combined effects by adjusting for specific covariates. RESULTS: After adjusting for covariates, short sleep duration (< 7 h) (OR = 0.53; 95% CI [ 0.30, 0.92]) and OSA risk (OR = 0.58; 95% CI [0.32, 0.83]) were negatively associated with better CVH (ideal vs. intermediate; intermediate vs. poor), respectively. For HD patients with both short sleep duration and OSA risk, the odds of ideal CVH metrics were reduced by 72% (odds ratio 0.28 [95% CI 0.13, 0.60]). CONCLUSIONS: Short sleep duration and OSA risk are separately and jointly associated with poor CVH in hemodialysis patients. Suitable interventions for sleep may minimize the risk of developing cardiovascular disease.

Recent Advances in the Preparation and Application of Biochar Derived from Lignocellulosic Biomass: A Mini Review.

With the rapid growth in the global population and the accelerating pace of urbanization, researching and developing novel strategies for biomass utilization is significant due to its potential for use in renewable energy, climate change mitigation, waste management, and sustainable agriculture. In this environmental context, this review discusses the recent advances in biomass conversion technologies for biochar production, including the first carbonization process and the subsequent activation methods of the biochar derived from lignocellulosic biomass (LBC). Parallel to this, this review deals with other essential parameters in biochar production, such as feedstock types, reaction environments, and operating conditions in the pyrolysis process, to determine the production and composition of LBC. Moreover, the wide-ranging applications of LBC in areas such as adsorption, catalysts, and energy storage are discussed, offering sustainable and environmentally friendly alternatives while reducing reliance on traditional energy sources and mineral resources, thereby providing practical solutions to environmental and energy challenges. Overall, this review not only provides a comprehensive comparative analysis of different LBC preparation methods, but also facilitates a deeper understanding of the advantages and limitations of these methodologies when it comes to developing high-value materials for sustainable applications.

Amino- and Alkoxybenziodoxoles: Facile Preparation and Use as Arynophiles.

We report here on the facile synthesis of amino- and alkoxy-λ3-iodanes supported by a benziodoxole (BX) template and their use as arynophiles. The amino- and alkoxy-BX derivatives can be readily synthesized by reacting the respective amines or alcohols with chlorobenziodoxole in the presence of a suitable base. Unlike previously known nitrogen- and oxygen-bound iodane compounds, which have primarily been employed as electrophilic group transfer agents or oxidants, the present amino- and alkoxy-BX reagents manifest themselves as nucleophilic amino and alkoxy transfer agents toward arynes. This reactivity leads to the aryne insertion into the N-I(III) or O-I(III) bond to afford ortho-amino- and ortho-alkoxy-arylbenziodoxoles, iodane compounds nontrivial to procure by existing methods. The BX group in these insertion products exhibits excellent leaving group ability, enabling diverse downstream transformations.