bluuebunny/crossref_metadata_2025 huggingface dataset:
NIR‐Activable Charge Transfer Agents for Synergistic Photoimmunotherapy
Authors: Wang Chu , Zhong Wenbin , Sun Xiaohuan , Guo Jingjing , Chen Yun , Zhao Yue , Han Jie , Zhao Yanli
Published: September 2024

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has become an attractive tumor treatment modality, yet the facile design of photoimmunotheranostic agents with efficient near infrared (NIR) light‐absorbing and immune‐activating capabilities remains a tremendous challenge. Herein, we developed a NIR‐activable organic charge transfer complex (CTC), with perylene (PER) as the electron donor and 4,5,9,10‐tetrabromoisochromeno [6,5,4‐def]isochromene‐1,3,6,8‐tetraone (Br4NDI) as the electron acceptor. Through further supramolecular assembly, the PER‐Br4NDI nanoparticle (PBND NP) for spatiotemporally controlled photoimmunotherapy was constructed. The PBND NP exhibits superb NIR absorption, robust intermolecular charge transfer, and enhanced intersystem crossing. Upon NIR photoirradiation, the PBND NP effectively exerts photothermal and photodynamic effects with a remarkable photothermal conversion efficiency of 63.5 % and a high reactive oxygen species generation capability, which not only directly ablates primary tumors, but also dramatically suppresses distant tumor growth via promoted immunogenic cell death. Moreover, programmed cell death protein 1 antibody acts synergistically to block immune evasion and ultimately enhances cancer treatment efficacy. This work therefore sheds light on the design of organic CTCs for synergistic photoimmunotherapy.
Emulating “Curvature‐Enhanced Adsorbate Coverage” for Superconformal and Orientated Zn Electrodeposition in Zinc‐ion‐Batteries
Authors: Wang Huibo , Liu Yi , Zhu Mengyu , Chen Yuejin , Chen Danling , Lin Zhimin , Wang Kexuan , Xu Zhu , Chen Shi , Xing Guichuan , Malyi Oleksandr I. , Tang Yuxin , Zhang Yanyan
Published: September 2024

Uneven Zn deposition and unfavorable side reactions have prevented the reversibility of the Zn anode. Herein, we design a rearranged (002) textured Zn anode inspired by a traditional curvature‐enhanced adsorbate coverage (CEAC) process to realize the highly reversible Zn anode. The rearranged (002) textured structure directs superconformal Zn deposition by controlling the spatial deposition rate of the rearranged crystal planes, thereby promoting bottom‐up “superfilling” of the 3D Zn skeletons. Meanwhile, our designed anode also induces the epitaxial Zn deposition, alleviating the parasitic reactions owing to the lowest surface energy of the (002) plane. Attributed to these superiorities, uniform and oriented Zn deposition can be obtained, exhibiting an ultra‐long lifespan over 479 hrs at an ultrahigh depth of discharge (DOD) of 82.12 %. The Zn|Na2V6O16 ⋅ 3H2O battery delivers an improved cycling performance, even at a high area capacity of 5.15 mAh/cm2 with a low negative/positive (N/P) capacity ratio of 1.63. The superconformal deposition approach for Zn anodes paves the way for the practical application of high‐performance zinc‐ion batteries.
Chemo‐Enzymatic Depolymerization of Functionalized Low‐Molecular‐Weight Polyethylene
Authors: Oiffer Thomas , Leipold Friedemann , Süss Philipp , Breite Daniel , Griebel Jan , Khurram Muhammad , Branson Yannick , de Vries Erik , Schulze Agnes , Helm Christiane A. , Wei Ren , Bornscheuer Uwe T.
Published: September 2024

Polyethylene (PE) is the most commonly used plastic type in the world, contributing significantly to the plastic waste crisis. Microbial degradation of PE in natural environments is unlikely due to its inert saturated carbon‐carbon backbones, which are difficult to break down by enzymes, challenging the development of a biocatalytic recycling method for PE waste. Here, we demonstrated the depolymerization of low‐molecular‐weight (LMW) PE using an enzyme cascade that included a catalase‐peroxidase, an alcohol dehydrogenase, a Baeyer Villiger monooxygenase, and a lipase after the polymer was chemically pretreated with m‐chloroperoxybenzoic acid (mCPBA) and ultrasonication. In a preparative experiment with gram‐scale pretreated polymers, GC‐MS and weight loss determinations confirmed ~27 % polymer conversion including the formation of medium‐size functionalized molecules such as ω‐hydroxycarboxylic acids and α,ω‐carboxylic acids. Additional analyses of LMWPE‐nanoparticles using AFM showed that enzymatic depolymerization reduced the sizes of these mCPBA‐ and enzyme‐treated LMWPE‐nanoparticles. This multi‐enzyme catalytic concept with distinct chemical steps represents a unique starting point for future development of bio‐based recycling methods for polyolefin waste.
Visible‐Light‐Driven Solid‐State Fluorescent Photoswitches for High‐Level Information Encryption
Authors: Han Zhiyuan , He Meixia , Wang Gang , Lehn Jean‐Marie , Li Quan
Published: September 2024

Developing visible‐light‐driven fluorescent photoswitches in the solid state remains an enormous challenge in smart materials. Such photoswitches are obtained from salicylaldimines through excited‐state intramolecular proton transfer (ESIPT) and subsequent cis‐trans isomerization strategies. By incorporating a bulky naphthalimide fluorophore into a Schiff base, three photoswitches achieve dual‐mode changes (both in color and fluorescence) in the solid state. In particular, the optimal one generates triple fluorescence changing from green, to yellow and finally to orange upon visible‐light irradiation. This switching process is fully reversible and can be repeated at least 10 times without obvious attenuation, suggesting its good photo‐fatigue resistance. Mechanism studies reveal that the naphthalimide group not only enables the tuning of multicolor with an additional emission, but also induces a folded structure, reducing molecular stacking and facilitating ESIPT and cis‐trans isomerization. As such, photopatterning, ternary encoding and transient information recording and erasing are successfully developed. The present study provides a reliable strategy for visible‐light‐driven fluorescent photoswitches, showing implications for advanced information encryption materials.
Stabilizing Hydrogen Radicals in Two‐Dimensional Cobalt‐Copper Mesoporous Nanoplates for Complete Nitrate Reduction Electrocatalysis to Ammonia
Authors: Han Chenyu , Sun Lizhi , Han Shu , Liu Ben
Published: September 2024

Ambient electrochemical reduction of waste nitrate (NO3−) represents an alternative green route for sustainable ammonia (NH3) electrosynthesis in water. Despites some encouraged achievements, sluggish eight electron and nine proton reduction routes that involve multi‐step hydrogenation pathways have severely hindered their NH3 Faradaic efficiency (FENH3) and yield rate. Herein, we develop a robust two‐dimensional mesoporous cobalt‐copper (meso‐CoCu) nanoplate electrocatalyst that delivers excellent performance of complete NO3− reduction reaction (NO3RR), including superior FENH3 of 98.8 %, high NH3 yield rate of 3.39 mol h−1 g−1 and energy efficiency of 49.8 %, and good cycling stability. Mechanism investigations unveil that active hydrogen (*H) radicals produced from water splitting on Co sites spillover to adjacent Cu sites and further stabilize within confined mesopores, which kinetically promote its coupling hydrogenation reactions of nitrogen intermediates and thus facilitate complete NO3RR for favorable NH3 electrosynthesis. Moreover, meso‐CoCu nanoplates perform well as a bifunctional electrocatalyst in the two‐electrode coupling system that concurrently synthesizes NH3 from NO3− at cathode and 2,5‐furanedicarboxylic acid from 5‐hydroxymethylfurfural at anode. This work in stabilizing *H radicals in mesoporous microenvironment provides some insights applied to various hydrogenation reactions for selective electrosynthesis of high value‐added chemicals in water.
Electrochemically Driven Asymmetric Hydrogenation of Aromatic Ketones by Noyori–Ikariya Catalyst
Authors: Zhu Jing‐Wei , Wang Le‐Ting , Wang Ya‐Li , Chen Lei‐Bing , Lu Jia‐Xing , Wang Huan
Published: September 2024

The electrochemically driven asymmetric hydrogenation of 2,2,2‐trifluoroacetophenone was performed using a Noyori–Ikariya catalyst, yielding a 97% product yield and a 47% enantiomeric excess (ee) with a charge input of only 0.5 F/mol. In comparison, the ethoxylate anion generated by the electroreduction of the solvent, EtOH, can efficiently drive the transfer hydrogenation of Ru catalysts more effectively than organic bases. After optimizing the electrolysis conditions, this method has been successfully extended to other aromatic ketones, including heterocyclic aromatic ketones and the base‐sensitive substrate ethyl benzoylformate, with yields ranging from 71% to 97% and ee values ranging from 55% to 82%. A possible reaction mechanism was proposed.
Aggregation‐Enhanced Photodynamic Activity of Organometallic Ru(II)–Arene Complexes
Authors: Bu Jingjing , Xu Zhiwei , Sun Yanyan , Gao Ya , Zhao Jian , Xu Gang
Published: September 2024

Organometallic Ru(II)–arene complexes have emerged as potential chemotherapeutic agents for improved cancer treatment. However, the application of Ru(II)–arene complexes as photosensitizers has been rarely explored. In consideration of their excellent biological performance, herein, three Ru(II)–arene complexes 1–3 bearing 2,3,8,9,14,15‐hexamethyl‐5,6,11,12,17,18‐hexaazatrinapthalene (HATN‐Me6) as acceptor ligand have been designed and investigated as potential photosensitizers. Distinctively, complexes 1–3 produced negligible singlet oxygen (1O2) generation in DMF. The mechanism investigations indicated that the large change in equilibrium displacement between the excited and ground states rather than narrow energy gap results in the increased vibrational wave function overlap and non‐radiative decay rate. Remarkably, complexes 1–3 induced greatly enhanced 1O2 generation efficiency in an aggregated state due to the suppression of the non‐radiative decay process, implying that the electronic structures of excited states play an essential role in the photochemical properties and functions of the organometallic Ru(II)–arene complexes. The biological evaluation showed that complexes 1–3 exhibited potent photocytotoxicity against cancer cells, highlighting that organometallic Ru(II)–arene scaffolds are potential platforms for the fabrication of efficient photosensitizers.
Development of morphine analgesia using biocompatible synthesized molecular imprinted hydrogel based on tragacanth gum
Authors: Hassanzadeh Marjan , Ghaemy Mousa , Ahmadi Shamseddin , Amininasab S. Mojtaba , Miraki Fatemeh
Published: September 2024

A novel molecular imprinted hydrogel using tragacanth gum (MITMIH) was synthesized for extending morphine analgesic efficacy by controlled release. The characterized MITMIH was used as a new morphine carrier that can increase analgesic time window after its single injection in mice. During in vitro optimization, the MITMIH showed maximum adsorption capacity (~113 mg g−1) at pH = 6.5 after 20 min immersion (400 μM initial morphine concentration, 10 mg MITMIH). During in vivo test, we examined the analgesic effect in mice by dissolving morphine in physiologic saline or by loading on MITMIH. The results of a single injection revealed that morphine‐loaded MITMIH shifted the time profile of morphine analgesia from 123.4 to 257.6 min. This indicates almost 100% efficacy in the controlled release of the drug during 5 h after the injection. Furthermore, cytotoxicity and mitochondrial membrane potential test was evaluated against normal rat kidney epithelial (NRK) and Rat Dermal Fibroblasts (RDF). The results confirmed that the MITMIH could be considered as a potential carrier increasing length of morphine analgesia after the first single injection without any cytotoxicity and negative effect on cell tissues. This may in turn reduce repeated use of the drug to achieve satisfactory analgesia in patients with chronic pain.
PVA‐based Hydrogel Materials for Underwater Energy Storage and Underwater Sensing
Authors: Zhou Peidi , Xu Bingjie , Feng Haihang , Luo Zhiling , Weng Mingcen
Published: September 2024

As human exploration of marine continues to expand, the demand for underwater devices is also increasing. The unique properties of hydrogel materials make them well‐suited for underwater applications. We propose a multi‐functional polyvinyl alcohol (PVA) – NaCl @ Polyaniline (PANI) (PNP) hydrogel, which is characterized by easy fabrication, integrated structure, and flexibility, and can be directly applied in the fields of underwater energy storage and underwater sensing. Solid‐state supercapacitors fabricated by the PNP hydrogel, due to integrated and all‐solid‐state design, can be charged and discharged underwater without encapsulation. What's more, the PNP supercapacitor can maintain a capacitance retention rate of over 90 % after 5,000 cycles in simulated seawater, eliminating concerns about the hydrogel's dehydration when used underwater. The PNP hydrogel with an integrated three‐layer structure can also be applied to the capacitive pressure sensors, which can also be directly used in underwater environments without the need for encapsulation, significantly reducing the structural complexity and preparation steps of the device. Finally, we demonstrate a “supercapacitor module” with a voltage window greater than 1.6 V created by directly connecting multiple PNP supercapacitors in series, as well as an underwater intelligent glove, providing new solutions for underwater energy storage and underwater wearable sensing applications.
The moderation effect of morphological awareness on the relationship between word detection skills and reading comprehension in Chinese children with and without dyslexia
Authors: Wang Li‐Chih , Liu Duo , Xu Zhengye
Published: September 2024

This study aimed to investigate the moderating effect of morphological awareness on the relationship between word detection skills and reading comprehension in Chinese children with and without dyslexia. The study included 116 Chinese children in third to sixth grades, with 60 children diagnosed with dyslexia and 56 matching typically developing children. ANCOVAs revealed significant group differences in word detection skills and morphological awareness, with children with dyslexia performing significantly worse than their typically developing peers. Partial correlation analyses showed significant correlations between reading comprehension and morphological awareness in typically developing children and between reading comprehension and both word detection skills and morphological awareness in children with dyslexia. Moderation analyses revealed that morphological awareness significantly moderated the relationship between word detection skills and reading comprehension in both groups. For typically developing children, the relationship was significant at higher levels of morphological awareness, while for children with dyslexia, the relationship was significant at lower levels of morphological awareness. The findings suggest that word detection skills may serve as a compensatory mechanism for children with dyslexia when morphological awareness is at lower levels, highlighting the need for targeted interventions and individualised approaches to reading instruction.
Sustainable solutions for direct TLC enantioseparation with in‐home thought‐out, prepared/modified chiral stationary phases
Authors: Bhushan Ravi
Published: September 2024

TLC is used globally, yet less attention has been paid to TLC (in enantioseparation) despite its advantages. The present paper describes/reviews successfully practiced direct approaches of ‘chiral additive in achiral stationary phase’ (as an application of in‐home thought out, prepared, tested, and modified chiral stationary phase), ‘pre‐mixing of chiral reagent with the enantiomeric mixture’ (an approach using both achiral phases during chromatographic separation) and ‘chiral additive in mobile phase’, and chiral ligand exchange for enantioseparation of DL‐amino acids, their derivatives, and some active pharmaceutical ingredients. It provided efficient enantioseparation, quantitative determination, and isolation of native forms via in‐situ formation of non‐covalent diastereomeric pair. The mechanism of enantioseparation in these approaches has been discussed along with the isolation and establishment of the structure of diastereomers. This may help chemists gain useful insights into fields outside their specialization and the experts get brief accounts of recent key developments, providing solutions for sustainable development of less expensive methods for control of enantiomeric purity and isolation of native enantiomers.
RETRACTED: The interplay of corporate governance, internal audit effectiveness, and sustainable financial reporting quality in Tanzanian commercial banks
Authors: Ally Zawadi
Published: September 2024

This paper investigates the relationship between internal audit effectiveness, corporate governance attributes, and sustainable financial reporting quality within Tanzanian commercial banks. Grounded by agency cost theory to provide new insights into the determinants of financial reporting quality in a developing country context. A cross‐sectional and correlational research design was employed, utilizing a structured questionnaire distributed to 150 respondents across a representative sample of Tanzanian commercial banks. Data analysis was conducted using multiple linear regression techniques, with comprehensive diagnostic tests to ensure the robustness of the findings. The results indicate that larger board sizes and proactive board role performance significantly enhance financial reporting quality, reflecting the importance of strong governance structures. Board independence showed a significant impact on financial reporting quality, suggesting that board independence with active engagement contributes to financial reporting quality. Internal audit quality also emerged as a critical predictor of reliable financial reporting, underscoring the role of internal audit in promoting transparency and accountability. These findings contribute to the ongoing debate in corporate governance literature by providing evidence from a developing country perspective, highlighting the nuanced roles of governance and audit in shaping financial reporting quality. This study fills a key gap in the literature by focusing on the Tanzanian banking sector, offering practical recommendations for policymakers and practitioners aimed at enhancing the integrity of financial reporting. Policymakers should emphasize board independence and the active involvement of board members and strengthen internal audit functions to improve reporting transparency and accountability.
A CRISPR mediated point‐of‐care assay for the detection of mucosal calprotectin in an animal model of ulcerative colitis
Authors: Chia Selena , Guo Tianruo , Goldys Ewa M. , Payne Sophie C. , Duan Wenlu , Lovell Nigel H. , Shivdasani Mohit N. , Deng Fei
Published: September 2024

Inflammatory bowel disease (IBD) is a chronic disorder associated with inflammation in the gastrointestinal tract, leading to a range of debilitating symptoms. Fecal calprotectin is an established biomarker for ulcerative colitis (UC), one of the main IBD diseases, which provides indications of the presence and severity of inflammation in the digestive tract. Enzyme‐Linked Immunosorbent Assay (ELISA) as a gold standard approach for fecal calprotectin detection is time‐consuming and impractical in point‐of‐care settings. Moreover, obtaining fecal samples from patients is challenging and inhibits longitudinal monitoring. To address these specific problems, we have developed a novel approach for detecting calprotectin which leverages clustered regularly interspaced short palindromic repeats (CRISPR)/Cas technology. We successfully developed a portable tube‐based CRISPR/Cas assay for point‐of‐care testing of calprotectin. This assay showed a detection range from 1 to 10,000 ng/ml (over 4 log units), using both fluorescent and colorimetric analytical techniques. The established assay was further validated through measurements in mucosal samples obtained in an anesthetised preclinical rodent model of UC, with 2–3 times higher calprotectin concentration detected in UC rat samples compared to that of healthy control animals. This point‐of‐care test may provide a rapid, precise, and user‐friendly approach for the diagnosis and monitoring of IBD through mucosal sample testing.
Hyperspectral imaging facilitating resect‐and‐discard strategy through artificial intelligence‐assisted diagnosis of colorectal polyps: A pilot study
Authors: Peng Cheng , Tian Chong Xuan , Mu Yijun , Ma Mingjun , Zhang Zhenlei , Wan Meng , Liu Jing , Li Zhen , Zuo Xiuli , Li Wei , Li Yanqing
Published: September 2024

Background and Aims

The resect‐and‐discard strategy for colorectal polyps based on accurate optical diagnosis remains challenges. Our aim was to investigate the feasibility of hyperspectral imaging (HSI) for identifying colorectal polyp properties and diagnosis of colorectal cancer in fresh tissues during colonoscopy.

Methods

144,900 two dimensional images generated from 161 hyperspectral images of colorectal polyp tissues were prospectively obtained from patients undergoing colonoscopy. A residual neural network model was trained with transfer learning to automatically differentiate colorectal polyps, validated by histopathologic diagnosis. The diagnostic performances of the HSI‐AI model and endoscopists were calculated respectively, and the auxiliary efficiency of the model was evaluated after a 2‐week interval.

Results

Quantitative HSI revealed histological differences in colorectal polyps. The HSI‐AI model showed considerable efficacy in differentiating nonneoplastic polyps, non‐advanced adenomas, and advanced neoplasia in vitro, with sensitivities of 96.0%, 94.0%, and 99.0% and specificities of 99.0%, 99.0%, and 96.5%, respectively. With the assistance of the model, the median negative predictive value of neoplastic polyps increased from 50.0% to 88.2% (p = 0.013) in novices.

Conclusion

This study demonstrated the feasibility of using HSI as a diagnostic tool to differentiate neoplastic colorectal polyps in vitro and the potential of AI‐assisted diagnosis synchronized with colonoscopy. The tool may improve the diagnostic performance of novices and facilitate the application of resect‐and‐discard strategy to decrease the cost.
Unraveling the impact of lysosomal dysfunction on myeloproliferative neoplasm
Authors: Yoon Hyundong , Lee Dohoon , Song Seulki , Koo Bonil , Park Jihyun , Kim Tae Kon , Kim Sun , Kim Sheehyun , Hong Junshik , Byun Ja Min , Shin Dong‐Yeop , Kim Inho , Koh Youngil , Yoon Sung‐Soo
Published: September 2024

Background

Lysosomal dysfunction (LD) impacts cytokine regulation, inflammation, and immune responses, influencing the development and progression of cancer. Inflammation is implicated in the pathogenesis of myeloproliferative neoplasm (MPN). With a hypothesis that LD significantly contributes to MPN carcinogenesis by inducing abnormal inflammation, our objective was to elucidate the pathophysiological mechanisms of MPN arising from an LD background.

Methods

Genotyping of the LD background was performed in a cohort of MPN patients (n = 190) and healthy controls (n = 461). Logistic regression modeling, utilizing genotype data, was employed to estimate the correlation between LD and MPN. Whole transcriptome sequencing (WTS) (LD carriers = 8, non‐carriers = 6) and single‐cell RNA sequencing data (LD carriers = 2, non‐carriers = 2, healthy controls = 2) were generated and analyzed.

Results

A higher variant frequency of LD was observed in MPN compared to healthy controls (healthy, 4.9%; MPN, 7.8%), with the highest frequency seen in polycythemia vera (PV) (odds ratio = 2.33, p = 0.03). WTS revealed that LD carriers exhibited upregulated inflammatory cytokine ligand–receptor genes, pathways, and network modules in MPNs compared to non‐carriers. At the single‐cell level, there was monocyte expansion and elevation of cytokine ligand–receptor interactions, inflammatory transcription factors, and network modules centered on monocytes. Notably, Oncostatin‐M (OSM) consistently emerged as a candidate molecule involved in the pathogenesis of LD‐related PV.

Conclusions

In summary, an LD background is prevalent in MPN patients and leads to increased cytokine dysregulation and inflammation. OSM, as one of the potential molecules, plays a crucial role in PV pathogenesis by impairing lysosomal function.
Predicting treatment success and failure using routine outcome data: The role of therapist effects in dynamic predictive modelling
Authors: Mahon Daryl , Minami Takuya , Brown Jeb
Published: September 2024

Background

The goal of this research was to identify how early in psychotherapy a reliable prediction regarding the probability of premature termination, treatment failure or treatment success can be made, and which variables are most predictive. This research breaks new ground by including data on each clinician's historical outcomes (therapist effects) to explore to what degree predictions and decision rules might differ with therapist effectiveness.

Materials & Methods

Data was drawn from a large online database of clients regularly completing self‐report outcome questionnaires. The sample included clinicians (n = 1020) treating clients (n = 68,690) with an intake score in the clinical range during a treatment episode of between 2 and 10 sessions. Variables available at the first session and later sessions were tested for predictive validity for status at subsequent sessions using general linear regression models and logistic regression models.

Results

The results suggest that therapy outcomes can be predicted as early as the second session with a good degree of accuracy, 65%. The analyses revealed that predictions made as early as the second session remain valid even for clients taking up to 10 sessions to complete treatment. Adding therapist effects to the predictive model provides a much more nuanced understanding of the results. By session two, therapists in the top quartile demonstrate effect sizes comparable to the effect sizes of bottom quartile therapists at session ten.

Conclusion

The probability of client success, failure or early termination varies significantly depending on the clinician. Implications for training and supervision are discussed.
An exploration of psychotherapists' readiness to join the psychedelic renaissance
Authors: Scanlon Siobhan , Donohue Gráinne
Published: September 2024

Background

Research on psychedelics centres on two key areas: the action of psychedelics on the brain and the protocol for delivering therapy. There is little research that considers the implications of this novel therapy on the therapist delivering the treatment. This research study sought to explore this.

Aim and Objectives

The aim of this research was to explore the considerations for psychotherapists interested in delivering psychedelic therapy. Objectives were to examine the therapeutic conditions needed for effective outcomes, to explore the perceived differences between the practice of standard psychotherapy and psychedelic therapy and to determine the challenges for therapists working in the field.

Method

Six semi‐structured interviews were conducted with therapists who work in clinical or retreat settings. Interview transcripts were analysed using qualitative thematic analysis.

Findings

Three themes emerged that highlight the importance of preparation for effective clinical outcomes, the differences in standard and psychedelic practice and the personal and professional implications for therapists.

Conclusions

The results highlighted challenges and revealed the need for clear protocols for integrating psychedelics into psychotherapy practice.
Aromatic Abietane‐Type Diterpenoids from the Roots of Salvia prattii and their Protective Activity Against Alcoholic Liver Disease
Authors: Zhang Ming , Yang Yi‐Ran , Chen Yan‐Fang , Ren Fu‐Cai , Pu Xiang‐Dong , Shen Chuan‐Pu
Published: September 2024

Eighteen aromatic abietane‐type diterpenes, including three previously unreported compounds, Salkanoids A−C (1–3), were isolated from the roots of Salvia prattii. Their stuctures were extensively elucidated using 1D/2D NMR, high‐resolution electrospray ionization mass spectrometry (HRESIMS) data, and ECD calculation. Among these, compounds 1, 6 and 7 belong to a class of diterpenes featuring a [5, 5]‐oxaspirolactones moiety, a rare structure isolated from the Salvia plants. All the isolates were assessed for their protective effects against alcoholic liver disease using ethanol‐induced AML‐12 cell lines. The findings revealed that compounds 2, 5, 8 and 15 demonstrated potential protective activity.
Synthesis and Acetylcholinesterase Inhibitory Activity of Novel Trilaciclib Analogs
Authors: Muzychka Liubov , Muzychka Oksana , Smolii Oleg
Published: September 2024

Trilaciclib is a CDK4/6 inhibitor, used to treat the bone marrow damage in chemotherapy patients. A series of thirteen novel structural trilaciclib analogs was obtained to evaluate their activity against acetylcholinesterase. An effective method for the synthesis of 4,7‐substituted 8,9‐dihydropyrazino[1’,2’:1,5]pyrrolo[2,3‐d]pyrimidine derivatives from a new methyl 4‐chloro‐7H‐pyrrolo[2,3‐d]pyrimidine‐6‐carboxylate was developed. Most of the synthesized pyrazino[1’,2’:1,5]pyrrolo[2,3‐d]pyrimidine derivatives inhibited acetylcholinesterase in the micromolar range. The obtained data can be used for designing more potent acetylcholinesterase inhibitors with the pyrazino[1’,2’:1,5]pyrrolo[2,3‐d]pyrimidine scaffold.
Isolation of Novel Compounds from Lepidium sativum Seeds and Evaluation of Their Potential Anti‐Tumor Activity
Authors: Shybyray Yergazy , Kaiyrkulova Aida , Zhao Hai‐Qing , Jenis Janar , Aisa Haji Akber , Li Jun
Published: September 2024

Four undescribed compounds including a pair of enantiomers of a dihydroarylnaphthalene lignan [(±)−1], an arylnaphthalene lignan (2), and an indoleacetic acid ester (3), together with four known compounds (4–7), were isolated from the seeds of Lepidium sativum. Their structures were identified by HRMS and NMR spectroscopic data, and the absolute configuration of these compounds were assigned by ECD data in combination with quantum chemical calculations. Compound (−)−1 had weak inhibitory activity against HeLa cell line with an IC50 value of 60.23±3.51 μM, and compound (+)−1 presented moderate inhibitory effect against HeLa cell line with an IC50 value of 19.99±1.00 μM (IC50 value of the positive control was 0.40±0.02 μM).
Discovery of Arylpiperazines with Broad‐Spectrum Antimicrobial Activity and Favorable Pharmacokinetic Profiles
Authors: da Silva Oliveira Douglas Davison , Sousa Silva Nagela Bernadelli , Jacques Dit Lapierre Thibault Joseph William , Lemes de Souza Sara , Ferreira Brito Nícolas Peterson , Cassiano Martinho Ana Clara , Clemente Dias Renieidy Flávia , Nascimento Farago Danilo , Michelan‐Duarte Simone , Consolin Chelucci Rafael , de Moura Lodi Cruz Mariza Gabriela Faleiro , de Melo Resende Daniela , Andricopulo Adriano D. , Fonseca Murta Silvane Maria , Ferreira Leonardo L. G. , Gomes Martins Carlos Henrique , de Oliveira Rezende Júnior Celso
Published: September 2024

Microorganisms can induce diseases with significant clinical implications for human health. Multidrug‐resistant microorganisms have been on the rise worldwide over the past few decades, and no new antibiotics have been introduced to the market in a considerable amount of time. Such situation highlights the urgency of discovering new antimicrobial drugs to address this pressing issue. Therefore, the objective of this study was to identify bioactive compounds against 15 species of bacteria and 5 species of fungi of clinical relevance through in vitro screening of 58 synthetic compounds from four chemical classes of our internal library of synthetic compounds. Our findings highlight arylpiperazines 18, 20, 26, 27, and 29, and the aminothiazole 50, as potent broad‐spectrum antimicrobials (MICs=12.5–15.6 μg mL−1) against clinically relevant bacteria and fungi. Additionally, these compounds displayed low cytotoxicity against various host cells and a favorable in vitro pharmacokinetic profile for oral administration. Indeed, all six showed adequate lipophilicity, high gastrointestinal permeability, metabolic stability in human and mouse liver microsomes, and satisfactory aqueous solubility. Thus, they emerge as promising starting points for hit‐to‐lead studies towards new antibacterial and antifungal agents, especially against Staphylococcus epidermidis, Staphylococcus aureus, Lactobacillus paracasei and Candida orthopsilosis.
Photoactivable CRISPR for Biosensing and Cancer Therapy
Authors: Wang Siyuan , Wang Jiaqi , Li Baijiang , Zhang Jingjing
Published: September 2024

Photoactivable CRISPR technology represents a transformative approach in the field of genome editing, offering unprecedented control over gene editing with high spatial and temporal precision. By harnessing the power of light to modulate the activity of CRISPR components, this innovative strategy enables precise regulation of Cas proteins, guide RNAs, and ribonucleoprotein complexes. Recent advancements in optical control methodologies, including the development of photoactivable nanocarriers, have significantly expanded the potential applications of CRISPR in biomedical fields. This Concept highlights the latest developments in designing photoactivable CRISPR systems and their promising applications in biosensing and cancer therapy. Additionally, the remaining challenges and future trends are also discussed. It is expected that the photoactivable CRISPR would facilitate translating more precise gene therapies into clinical use.
Advanced laryngeal squamous cell carcinoma in an adolescent: A case and treatment considerations
Authors: Hunter Courtney J. , Moreno Mauricio A. , Strub Graham M.
Published: September 2024

Key Clinical Message

Pediatric laryngeal SCCa is a rare malignancy in childhood. High index of suspicion is critical to obtain timely tissue sample and diagnosis. Shared decision making is important when choosing treatment modalities for curative management, especially when working with adolescent patients.
Ca/Li Synergetic‐Doped Na0.67Ni0.33Mn0.67O2 to Realize P2‐O2 Phase Transition Suppression for High‐Performance Sodium‐Ion Batteries
Authors: Xiao Ke , Zhao Bangchuan , Bai Jin , Mao Yunjie , Wang Peiyao , Wang Siya , Zhu Xuebin , Sun Yuping
Published: September 2024

P2‐type layered transition metal oxide Na0.67Ni0.33Mn0.67O2 is considered as a promising cathode for advanced sodium‐ion batteries due to its high theoretical specific capacity. However, the P2‐type cathode suffers severe P2‐O2 phase transition during cycling process, resulting unsatisfactory cyclic stability and rate capability. Herein, a Ca/Li co‐doped P2‐type Na0.62Ca0.05Ni0.33Mn0.57Li0.10O2 (NCNMLO) cathode material was synthesized through a simple sol‐gel method. With the synergistic effect of Ca‐doping at Na sites and Li substitution at transition metal (TM) sites, the cathode achieves an excellent electrochemical performance due to the inhibited P2‐O2 phase transition and improved ion diffusion with Na+/vacancy disordering arrangement. The NCNMLO cathode exhibits a good cyclic stability with 70.8 % of capacity retention at 1 C after 200 cycles and excellent rate capability with 40.1 mAh g−1 at 20 C. The dual sites doping strategy provides an effective and simple approach for designing high‐performance layered oxide cathode materials for sodium‐ion batteries.
Pathway‐dependent Metallosupramolecular Polymerization Regulated by Ligand Geometry
Authors: Sutar Papri , Maisuls Iván , Fernández Zulema , Strassert Cristian A. , Fernández Gustavo
Published: September 2024

Understanding structure/property correlations in self‐assembly is a key but challenging requirement for developing functional materials. Herein, we explore the importance of ligand geometry to fine‐tune photophysical properties (MMLCT vs. MLCT excited states) and self‐assembly pathways in metallosupramolecular polymerization. To this end, we have designed two hydrophobic Pt(II) complexes, 1 and 2, containing a π‐extended bidentate bipyridine ligand with different substitution pattern, resulting in different molecular geometries (linear vs. V‐shaped). Detailed comparative studies revealed significant differences for both complexes in terms of their photophysical properties and self‐assembly pathways in non‐polar media. The V‐shaped topology of 1 enables facile face‐to‐face molecular stacking with a certain curvature leading to luminescent spherical assemblies exhibiting MMLCT states and short Pt⋅⋅⋅Pt contacts via a single‐step cooperative pathway. On the other hand, the higher preorganized linear topology of complex 2 induces a two‐step competitive self‐assembly process leading to the formation of one‐dimensional supramolecular polymers with slipped packing and MLCT‐originated emission. Our findings broaden the monomer scope for supramolecular polymerization and provide design guidelines for the realization of luminescent supramolecular assemblies.
Bifunctional Hexadentate Pyclen–Based Chelating Agent for Mild Radiofluorination in Aqueous Solution at Room Temperature with a Ga‐18F Ternary Complex
Authors: Dioury Fabienne , San Carine , Gnanalingam Gayathiri , Henoumont Céline , Rousselin Yoann , Haouz Ahmed , Shepard William , Hosten Benoît , Vijayakumar Kamsana , Laurent Sophie , Port Marc
Published: September 2024

Positron Emission Tomography (PET) is used in oncology for tumor diagnosis, commonly relying on fluorine‐18 (18F) emission detection. The conventional method of 18F incorporation on to probes by covalent bonding is harsh for sensitive biomolecules, which are nonetheless compounds of choice for the development of targeted probes. This study explores gallium–18F (Ga18F) coordination, a milder alternative method occurring in aqueous media at the final stage of radiosyntheses. Pyclen‐based chelating agents were proposed to capture (GaF) species at room temperature and pH≥5 making the radiofluorination process compatible with heat‐ and acid‐sensitive biomolecules. Highly promising results were obtained with the PC2A–based chelating agent LH2 derived from the new bifunctional PC2A–OAE–NCS compound. The solid‐state structure of GaF(L) was elucidated by X‐ray diffraction and revealed an unconventional heptacoordination of Ga(III). A high radiochemical conversion (RCC) of 86 % was achieved at room temperature, in water at pH 5 within 20 minutes. Stability studies showed the robustness of the GaF(L) complex in aqueous media for at least one day and at least one hour for the radiolabeled analog Ga18F(L). These findings demonstrated that PC2A‐based compounds are chelating agents of choice for (Ga18F) species, suggesting a real technological breakthrough for PET imaging and precision medicine.
6‐Methoxy‐2‐Naphthoate as a Standard Chromophore for Chiroptical Studies by Fluorescence‐Detected Exciton‐Coupled Circular Dichroism
Authors: Nagase Yui , Naka Yoshiki , Nehira Tatsuo
Published: September 2024

This study investigated the applicability of fluorescent chromophores for exciton‐coupled circular dichroism (ECCD) exploiting fluorescence‐detected circular dichroism (FDCD). FDCD had been previously reported useful in allowing the sensitive detection of ECCD in favorable conditions. However, fluorescence detection may prevent applications of the combined method especially when solutions are polarized in emission. Even without polarization of emission, FDCD deviates from circular dichroism (CD) in some cases when the fluorophore of interest interacts with nonfluorescent chromophore. Herein, it was confirmed that employing 6‐methoxy‐2‐naphthoate always yielded interpretable exciton‐coupled FDCD spectra even when coupling with nonfluorescent p‐substituted benzoates. The 6‐methoxy‐2‐naphthoate chromophore (6‐MN) is prescribed in special cases when only a small amount of sample is available for determining the absolute stereochemistry by the CD exciton chirality method observed by FDCD.
Assuring optimality in surrogate‐based optimization: A novel theorem and its practical implementation in pressure swing adsorption optimization
Authors: Rebello Carine Menezes , Costa Erbet Almeida , Sánchez Antonio Santos , Vides Fredy , Nogueira Idelfonso B. R.
Published: September 2024

Surrogate‐based optimization has gained significant traction in several engineering fields, given its ability to handle complex systems without significant computational burdens. However, surrogate models are approximations and may have limitations, including the possibility of artificial minima. The main contribution of this work is the derivation of a robustness test that guarantees the optimality of surrogate‐based optimization. The derivation of this metric is based on the universal approximation theorem. The full framework proposed in this work is also composed by a sampling sizing methodology to randomly select samples within a feasible operating region (FOR) resulting from the optimization population, reducing the computational cost of the analysis and avoiding biases in the robustness calculation. The applicability and importance of this methodology are demonstrated through a case study of a complex chemical process—a pressure swing adsorption (PSA) unit—which presents a high computational cost to solve optimization problems. The results highlight the need and importance of evaluating the optimality of surrogate‐based optimization schemes.
Short‐Cut Nitrification–Denitrification Spatial Combination Technology for Treating High‐Concentration Nitrogen‐Containing Wastewater: Influence of pH and Carbon Source
Authors: Chen Shuhe , Gao Yiman , Wang Cheng , Ma Xuemin , Xi Beidou , Tan Wenbing
Published: September 2024

Short‐cut nitrification (SCN) and denitrification (DN) technology is an efficient method for treating high‐concentration nitrogen‐containing wastewater. However, controlling the reaction conditions in single‐reactor systems is difficult. In this study, SCN and DN were performed in separate reactors to investigate the influence of pH on SCN and the effect of carbon sources on DN. The results revealed that a combination of SCN and DN achieved a total nitrogen removal efficiency of 84%. Within a specific pH range (6.5–9.0), the accumulation of nitrite during SCN exhibited an initial increase, followed by a decrease, reaching a maximum at pH 8.5. In addition, this study established two experimental groups to investigate the effect of carbon sources on DN. The blank group (without the addition of a carbon source) exhibited a chemical oxygen demand (COD) concentration of 5.1 mg/L, whereas the control group (sodium acetate used as the carbon source) exhibited a COD concentration of 118.6 mg/L. These results indicate a substantial improvement in DN efficiency with the addition of a carbon source.
Synthesis and Biological Evaluation of N‐(1H‐Indol‐6‐ylmethyl)benzenesulfonamide Analogs as Metabolic Inhibitors of Mitochondrial ATP Production in Pancreatic Cancer Cells
Authors: Brandeburg Zachary C. , Waheed Sakariyau A. , Derewonko Carina A. , Dunn Caroline E. , Pfeiffer Ethan C. , Flusche Ann Marie E. , Sheaff Robert J. , Lamar Angus A.
Published: September 2024

A library of 26 indolyl sulfonamides and 12 amide and ester analogs based upon the 6‐indolyl framework has been synthesized in an effort to target pancreatic cancer. The cytotoxicity of the indolyl sulfonamide compounds has been determined using a traditional (48‐h compound exposure) assay against 7 pancreatic cancer cell lines and 1 non‐cancerous cell line. The potential role of the compounds as metabolic inhibitors of ATP production was evaluated using a rapid screening (2‐h compound exposure) assay developed within our laboratories. The IC50 values of the active compounds were determined using the rapid assay and six compounds displayed an IC50 value <5 μM against one or more pancreatic cancer cell lines. The ester analogs also display activity as potential metabolic inhibitors of ATP production with four of the six compounds displaying an IC50 value <5 μM against one or more pancreatic cancer cell lines.
Synthesis and Structure‐Activity Relationship Analysis of 2‐Substituted‐1,2,4‐Triazolo[1,5‐a]Pyrimidin‐7‐Ones and their 6‐Carboxylate Derivatives as Xanthine Oxidase Inhibitors
Authors: Luna Giuseppe , Dolzhenko Anton V. , Mancera Ricardo L.
Published: September 2024

Hyperuricemia is characterised by high blood levels of uric acid, and it can degenerate into gout when monosodium urate crystals precipitate in joints and other tissues. Uric acid is produced during the catabolism of xanthine by the enzyme xanthine oxidase (XO), which is the primary therapeutic target in gout treatment. Current XO inhibitors approved to treat gout, such as allopurinol and febuxostat, suffer from serious adverse effects, creating the need for new drug molecules. Three libraries comprising 75 purine analogues were designed using a 1,2,4‐triazolo[1,5‐a]pyrimidine scaffold, synthesised and tested in vitro as potential XO inhibitors. The screening identified that 23 compounds exhibited better inhibitory activity than allopurinol, with 2‐(4‐isopropoxyphenyl)‐7‐oxo‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidine‐6‐carboxylic acid being 23 times more potent. Enzyme kinetics studies and molecular docking simulations were performed on the most active compounds to identify the mechanism of action and intermolecular interactions between the active site of XO and the inhibitors. The most potent compounds exhibited a mix‐type inhibition mechanism and were predicted to interact with the same amino acid residues as allopurinol. These novel purine analogues are promising hits for further new lead development among purine‐like drug XO inhibitors with therapeutic potential in the treatment of hyperuricemia and associated diseases.
Two birds, one stone? The risks and benefits of combined prenatal carrier screening and hereditary cancer screening
Authors: Ring Kari L.
Published: September 2024

There is growing literature for consideration of broader cancer genetic testing indications and the authors present a compelling argument for the combination of carrier screening and cancer genetic testing. As we employ any new strategy, we must ensure that the infrastructure is in place, that we provide equitable access to long‐term care, and that patient acceptability is at the forefront of these interventions.
Genotype‐by‐environment interaction for wheat falling number performance due to late maturity α‐amylase
Authors: Fairlie William , Hughes David , Cullis Brian , Edwards James , Kuchel Haydn
Published: September 2024

Late maturity α‐amylase (LMA) is known to reduce falling number (FN) in wheat (Triticum aestivum L.), similar to the effect of preharvest sprouting (PHS) and frost, which can result in grain parcels testing below trading thresholds. Hence, Grains Australia mandates that new Australian wheat cultivars must be at a low risk of LMA expression to receive a milling classification. The multi‐environment trial dataset contained 34 environments not affected by PHS or frost and was analyzed using a five‐factor analytic linear mixed model. Factor 1 accounted for 71.4% of the genetic variation in FN, factor 2 accounted for 8.8%, factor 3 accounted for 5.7%, factor 4 accounted for 3.5%, and factor 5 accounted for 3.1%. The interaction class (iClass) summary method was used to assist in the characterization of crossover genotype‐by‐environment interaction (G × E). Poorer FN performance was best observed in the “ppp” iClass, which indicated a minor, but significant, response to crossover G × E. The environment loadings for factor 1 were associated with mild ripening conditions, characterized by fewer days above 28°C, increased rainfall, and increased variation in daily maximum temperature and relative humidity. Factors 2 and 3 were associated with “cool shock” conditions, where the maximum temperature for 1 day was above 24°C followed by at least three consecutive days below 18°C during the grain fill period. This study provides further evidence of the crossover G × E present for FN associated with LMA, poor FN performance in genotypes that express higher levels of LMA, and the environmental conditions that contribute to LMA expression.