bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of Protein Phosphatase Magnesium-Dependent 1 (PPM1D) through Lentivirus-Mediated RNA Silencing Inhibits Colorectal Carcinoma Cell Proliferation
Authors: Yin Hongzhuan , Yan Zhaopeng , Liang Yichao , Liu Baolin , Su Qi
Published: June 2013

Colorectal cancer is one of the most common cancers in the world. Protein phosphatase magnesium-dependent 1δ (PPM1D) is aberrantly upregulated in many human carcinoma cells, and recent research has suggested that it could be a potential therapeutic target of cancer. However, the function of PPM1D in colorectal carcinoma cells is not well studied. To investigate the function of PPM1D in colorectal carcinoma, we used lentivirus-based RNA silencing to knock down the expression of PPM1D in RKO cells. We found that the lentivirus-mediated RNAi system efficiently decreased the expression level of endogenous PPM1D. Inhibiting PPM1D expression efficiently inhibited the proliferation and colony formation of RKO cells. Moreover, we found that PPM1D silencing led to G0/G1 cell-cycle arrest and the accumulation of cells at the sub-G1 phase. Furthermore, we found that PPM1D knockdown reduced the expression level of cyclinB1, inhibited ERK phosphorylation and activated the AKT signaling pathway. We found that PPM1D plays a crucial role in colorectal carcinoma cell proliferation and colony formation. Our work provides strong evidence suggesting that PPM1D is a potential therapeutic target of human colorectal cancers. Lentivirus-mediated PPM1D silencing is a promising gene therapeutic method to treat colorectal cancers.
Lack of Association between Cytotoxic T-Lymphocyte Antigen-4 −318C/T Polymorphism and Cancer Risk: A Meta-Analysis of Case-Control Studies
Authors: Xia Wei , Shi Rong , Zheng Wen-Ling , Ma Wen-Li
Published: June 2013

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is important for the down regulation of T-cell activation. Number of studies assessed the association between CTLA-4 −318C/T polymorphisms and cancer in different populations. However, the studies have provided conflicting results. We performed a meta-analysis to examine the association between CTLA-4 −318C/T polymorphisms and cancer susceptibility. Eligible studies were identified by searching several databases for relevant reports published up to September 30, 2012. Sixteen eligible studies with a total of 6190 patients and 6560 controls were included to summarize the association between CTLA-4 −318C/T polymorphisms and the risk of cancer. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Overall, no significant associations were found in all genetic models when all studies were pooled into the meta-analysis (for −318C/T polymorphisms as estimated using a fixed effect model: TT vs. (CC 1 CT), OR = 1.02, 95% CI = 0.83–1.24; (TT 1 CT) vs. CC, OR = 1.20, 95% CI = 1.00–1.44; TT vs. CC, OR = 1.09, 95% CI = 0.74–1.59; CT vs. CC, OR = 1.21, 95% CI = 1.00–1.46). In further subgroup analyses for the −318C/T polymorphisms, stratified by design of ethnicity, cancer types, solid tumors to non-solid tumors, epithelial tumors to non-epithelial tumors, no significant associations were found in any subgroup of the population. This meta-analysis strongly suggests that −318C/T polymorphisms in CTLA-4 are not associated with an increased risk of cancer.
Performance of salivary glands ultrasonography, shear wave elastography and their combined use for the diagnosis of primary and secondary Sjögren's syndrome
Authors: Cheng Lian , Yang Yan , Ma Ai‐Ju
Published: July 2024

Background

Sjögren's syndrome (SS) is a common rheumatic disease for which finding the right imaging tool remains a challenge.

Purpose

This study aimed to evaluate the performance of salivary gland ultrasonography (SGUS), shear wave elastography (SWE) and their combined use for the diagnosis of primary and secondary SS (pSS and sSS).

Methods

This retrospective study included patients with dry symptoms who underwent routine examinations between May 2019 and December 2023. Patients were categorized into the pSS (n = 41), sSS (n = 26), and control (n = 27) groups based on the American College of Rheumatology/European League Against Rheumatism classification criteria (2016). A comparison of SGUS and shear wave velocity (SWV) results was conducted among the three groups. The diagnostic capabilities of different ultrasound methods for SS were evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC) for specificity.

Results

Compared to the control group, both the pSS (1.80 ± 1.03 vs. 0.67 ± 0.48, p < 0.001) and the sSS (1.85 ± 0.88 vs. 0.67 ± 0.48, p < 0.001) groups exhibited significantly elevated SGUS scores. However, there was no statistically significant difference between the pSS and sSS groups (p = 0.849). The SWV values in both the pSS and sSS groups were significantly higher than those in the control group (all p < 0.001). The AUC for diagnosing SS using only SGUS scores was 0.823 (95% confidence interval [CI]: 0.731–0.894). Combining SGUS scores and SWV values resulted in improved diagnostic accuracy (AUC: 0.883, 95% CI: 0.801–0.940).

Conclusions

SGUS and SWE are pivotal in the diagnosis of Sjögren's syndrome, with their synergistic application poised to bolster diagnostic precision. This combined approach also furnishes substantial backing for the clinical assessment and management of Sjögren's syndrome.
Dose–exposure–efficacy response of intravenous immunoglobulin G 10% in multifocal motor neuropathy
Authors: Li Zhaoyang , Roepcke Stefan , Franke Ryan , Yel Leman
Published: July 2024

Objective

Multifocal motor neuropathy is a rare chronic immune‐mediated neuropathy with impaired grip strength representing a common symptom. While intravenous immunoglobulin G is an effective treatment for the disease, significant variation in treatment response has been observed but not well understood. This analysis characterized dose–exposure–response relationships in multifocal motor neuropathy, using grip strength as a clinical efficacy measure.

Methods

Serum immunoglobulin G trough concentrations and grip strength data for the more affected hand from a Phase 3, randomized, double‐blind, placebo‐controlled, crossover trial of intravenous immunoglobulin 10% in 44 patients with multifocal motor neuropathy (NCT00666263) were used to develop a population pharmacokinetic–pharmacodynamic model.

Results

The model adequately described the observed pharmacokinetic and pharmacodynamic data and relationships between intravenous immunoglobulin 10% dose, serum immunoglobulin G trough levels, grip strength, and inter‐patient variabilities in multifocal motor neuropathy. Model‐based simulations for various dosing regimens (0.4–2.0 g/kg every 2–4 weeks) indicated that ≥1.6 g/kg/month would achieve clinically meaningful improvements in grip strength (≥4 kg) in ≥70% of patients. More frequent dosing at an equivalent monthly dose led to a more consistent response in grip strength. Furthermore, splitting the dose over multiple days for high doses (>1 g/kg) did not impact grip strength.

Interpretation

These findings suggest that the majority of patients with multifocal motor neuropathy would respond rapidly to intravenous immunoglobulin 10% with a range of dosing regimens. Shorter dosing intervals may avoid the diminishing response seen with longer dosing intervals. Dose‐splitting provided similar outcomes while offering flexibility and convenience.
Organoids for Cancer Research: Advances and Challenges
Authors: Xin Miaomaio , Li Qian , Wang Dongyang , Wang Zheng
Published: July 2024

As 3D culture technology advances, new avenues have opened for the development of physiological human cancer models. These preclinical models provide efficient ways to translate basic cancer research into clinical tumor therapies. Recently, cancer organoids have emerged as a model to dissect the more complex tumor microenvironment. Incorporating cancer organoids into preclinical programs have the potential to increase the success rate of oncology drug development and recapitulate the most efficacious treatment regimens for cancer patients. In this review, four main types of cancer organoids are introduced, their applications, advantages, limitations, and prospects are discussed, as well as the recent application of single‐cell RNA‐sequencing (scRNA‐seq) in exploring cancer organoids to advance this field.
Dielectric Elastomer Network with Large Side Groups Achieves Large Electroactive Deformation for Soft Robotic Grippers
Authors: Dou Xiaorong , Chen Zheqi , Ren Fuhao , He Lijun , Chen Jianxiong , Yin Li‐Juan , Luo Yingwu , Dang Zhi‐Min , Mao Jie
Published: July 2024

Dielectric elastomer actuators (DEAs) face an acknowledged challenge: On the one hand, the majority of elastomers only achieve small electroactive deformation (<20%) in the absence of prestretch; on the other hand, rare elastomers capable of showing large electroactive deformation require relatively complicated processing and chemistry. This work addresses this challenge by fabricating an elastomer with a network of large side groups, which achieves a very large electroactive deformation (218%) without pre‐stretch. This elastomer can be rapidly and massively fabricated within a few min, by polymerizing a commercial monomer with a large alkyl side group. The large side groups in the polymer network repel each other and extend the load‐bearing strands, which results in a pronounced strain‐hardening behavior. This behavior helps the elastomer to get rid of electromechanical instability during actuation and hence to exhibit a large electro‐active deformation, a high energy density (>> human muscle), and a large output force (≈500 times self‐weight). the elastomer capable of manufacturing a soft electroactive gripper is demonstrated with large deformation, large force, and rapid response, which enables grasping fragile objects of various complex shapes in an agile away.
Highly Stretchable Thermoelectric Fiber with Embedded Copper(I) Iodide Nanoparticles for a Multimodal Temperature, Strain, and Pressure Sensor in Wearable Electronics
Authors: Yoon Kukro , Lee Sanghyeon , Kwon Chaebeen , Won Chihyeong , Cho Sungjoon , Lee Seungmin , Lee Minkyu , Lee Jinhan , Lee Hyeokjun , Jang Kyung‐In , Kim Byeonggwan , Lee Taeyoon
Published: July 2024

Thermoelectric (TE) fibers have excellent potential for multimodal sensor, which can detect mechanical and thermal stimuli, used in advanced wearable electronics for personalized healthcare system. However, previously reported TE fibers have limitations for use in wearable multimodal sensors due to the following reasons: 1) TE fibers composed of carbon or organic materials have low TE performance to detect thermal variations effectively; 2) TE fibers composed of rigid inorganic materials are not stretchable, limiting their ability to detect mechanical deformation. Herein, the first stretchable TE fiber‐based multimodal sensor is developed using copper(I) iodide (CuI), an inorganic TE material, through a novel fabrication method. The dense CuI nanoparticle networks embedded in the fiber allow the sensor to achieve excellent stretchability (maximum tensile strain of ≈835%) and superior TE performance (Seebeck coefficient of ≈203.6 µV K−1) simultaneously. The sensor exhibits remarkable performances in strain sensing (gauge factor of ≈3.89 with tensile strain range of ≈200%) and pressure sensing (pressure resolution of ≈250 Pa with pressure range of ≈84 kPa). Additionally, the sensor enables independent and simultaneous temperature change, tensile strain, and pressure sensing by measuring distinct parameters. It is seamlessly integrated into a smart glove, demonstrating its practical application in wearable technology.
Ultralong Blue Organic Room‐Temperature Phosphorescence Promoted by Green Assembly
Authors: Chen Zhong‐Yuan , Chen Zhaojun , Zhu Yu‐Qi , Zhuo Ming‐Zhi , Yang Guang‐Yao , Wang Xing‐Huo , Wu Ming‐Xue
Published: July 2024

In recent years, there is a growing interest in developing ultralong organic room‐temperature phosphorescence (ORTP) with lifetimes in the range of seconds. As one of the important three primary colors, ultralong blue ORTP is an indispensable core component in RTP regulation and application, however, the large Stokes shift characteristics pose certain challenges in developing ultralong blue ORTP. Here, a new family of blue phosphors are synthesized and ultralong blue ORTP are realized through crystal assembly in water and organic phase. Remarkably, compared to crystal materials obtained in organic phases, assembly materials obtained in water enabled long‐lived blue ORTP with lifetimes up to 2.3 s and phosphorescence quantum yield reached as high as 29.27%. In addition to the efficient and green assembly form, such dark blue ORTP materials possessed high thermal stability and flexible tunability. Moreover, the superiority of the selected assembly components is demonstrated by comparing them with polymer assembly and the proposed blue ORTP materials show great potential in an organic programmable information encryption/anti‐counterfeiting.
Paravertebrally‐Injected Multifunctional Hydrogel for Sustained Anti‐Inflammation and Pain Relief in Lumbar Disc Herniation
Authors: Deng Wenhao , Chen Jianpeng , Wang Xinli , Wang Qianliang , Zhao Lei , Zhu Yuzheng , Yan Jun , Zheng Yiran
Published: July 2024

Pain caused by lumbar disc herniation (LDH) severely compromises patients’ quality of life. The combination of steroid and local anesthetics is routinely employed in clinics to alleviate LDH‐induced pain. However, the approach only mediates transient efficacy and requires repeated and invasive lumbar epidural injections. Here a paravertebrally‐injected multifunctional hydrogel that can efficiently co‐load and controlled release glucocorticoid betamethasone and anesthetics ropivacaine for sustained anti‐inflammation, reactive oxygen species (ROS)‐removal and pain relief in LDH is presented. Betamethasone is conjugated to hyaluronic acid (HA) via ROS‐responsive crosslinker to form amphiphilic polymer that self‐assemble into particles with ropivacaine loaded into the core. Solution of drug‐loaded particles and thermo‐sensitive polymer rapidly forms therapeutic hydrogel in situ upon injection next to the herniated disc, thus avoiding invasive epidural injection. In a rat model of LDH, multifunctional hydrogel maintains the local drug concentration 72 times longer than free drugs and more effectively inhibits the expression of pro‐inflammatory cytokines and pain‐related molecules including cyclooxygenase‐2 (COX‐2) and prostaglandin E2 (PGE2). Therapeutic hydrogel suppresses the LDH‐induced pain in rats for 12 days while the equivalent dose of free drugs is only effective for 3 days. This platform is also applicable to ameliorate pain caused by other spine‐related diseases.
A General Strategy for Enhanced Photodynamic Antimicrobial Therapy with Perylenequinonoid Photosensitizers Using a Macrocyclic Supramolecular Carrier
Authors: Gao Zekun , Zheng Xiuli , Dong Xiangyu , Liu Weimin , Sha Jie , Bian Shuaishuai , Li Jian , Cong Huan , Lee Chun‐Sing , Wang Pengfei
Published: July 2024

Perylenequinonoid natural products are a class of photosensitizers (PSs) that exhibit high reactive oxygen species (ROS) generation and excellent activity for Type I/Type II dual photodynamic therapy. However, their limited activity against gram‐negative bacteria and poor water solubility significantly restrict their potential in broad‐spectrum photodynamic antimicrobial therapy (PDAT). Herein, a general approach to overcome the limitations of perylenequinonoid photosensitizers (PQPSs) in PDAT by utilizing a macrocyclic supramolecular carrier is presented. Specifically, AnBox·4Cl, a water‐soluble cationic cyclophane, is identified as a universal macrocyclic host for PQPSs such as elsinochrome C, hypocrellin A, hypocrellin B, and hypericin, forming 1:1 host–guest complexes with high binding constants (≈107 m
−1) in aqueous solutions. Each AnBox·4Cl molecule carries four positive charges that promote strong binding with the membrane of gram‐negative bacteria. As a result, the AnBox·4Cl‐PQPS complexes can effectively anchor on the surfaces of gram‐negative bacteria, while the PQPSs alone cannot. In vitro and in vivo experiments demonstrate that these supramolecular PSs have excellent water solubility and high ROS generation, with broad‐spectrum PDAT effect against both gram‐negative and gram‐positive bacteria. This work paves a new path to enhance PDAT by showcasing an efficient approach to improve PQPSs’ water solubility and killing efficacy for gram‐negative bacteria.
A Soldering Flux Tackles Complex Defects Chemistry in Sn‐Pb Perovskite Solar Cells
Authors: Zhou Wentao , Chen Yihua , Li Nengxu , Huang Zijian , Zhang Yu , Zhang Zhongyang , Guo Zhenyu , Yin Ruiyang , Ma Yue , Pei Fengtao , Xie Haipeng , Zai Huachao , Wang Lina , Qiu Zhiwen , Chen Qi , Zhou Huanping
Published: July 2024

Developing tin‐lead (Sn‐Pb) narrow‐bandgap perovskites is crucial for the deployment of all‐perovskite tandem solar cells, which can help to exceed the limits of single‐junction photovoltaics. However, the Sn‐Pb perovskite suffers from a large number of bulk traps and interfacial nonradiative recombination centers, with unsatisfactory open‐circuit voltage and the consequent device efficiency. Herein, for the first time, it is shown that abietic acid (AA), a commonly used flux for metal soldering, effectively tackles complex defects chemistry in Sn‐Pb perovskites. The conjugated double bond within AA molecule plays a key role for self‐elimination of Sn4+‐Pb0 defects pair, via a redox process. In addition, C═O group is able to coordinate with Sn2+, leading to the improved antioxidative stability of Sn‐Pb perovskites. Consequently, a ten‐times longer carrier lifetime is observed, and the defects‐associated dual‐peak emission feature at low temperature is significantly inhibited. The resultant device achieves a power conversion efficiency improvement from 22.28% (Ref) to 23.42% with respectable stability under operational and illumination situations.
Scanning‐Laser‐Based Microstereolithography of Microfluidic Chips with Micron Resolution
Authors: Rein Christof , Kamranikia Keynaz , Council Raymonde , Pezeshkpour Pegah , Kotz‐Helmer Frederik , Rapp Bastian E.
Published: July 2024

The constant improvement of stereolithography (SL) in terms of achievable resolution and printing time has sparked high expectations that SL will enable the rapid prototyping of truly microfluidic chips with features below 100 µm. However, most commercial high‐resolution stereolithography devices are based on Digital Light Processing (DLP) and thus sacrifice lateral printing size for resolution. Consequently, even 10 years after the advent of microstereolithography there is no commercialized 3D printing system that can effectively fulfill all the demands to replace soft lithography for microfluidic prototyping. In this work, for the first time, This study demonstrates that a commercial laser‐based stereolithography device is capable of manufacturing microfluidic chips with embedded channels smaller than 100 µm with a footprint of 7.24 × 0.3 cm2. A chip fabricated in poly(ethylene glycol) diacrylate (PEGDA) that can readily be used for fluid mixing, is presented in this study. This research shows that the accessibility of high‐resolution chips with footprints of several cm2, using laser‐based stereolithography, enables the manufacturing of truly microfluidic systems with high impact on prototyping and manufacturing.
A Review on 3D Printing Processes in Pharmaceutical Engineering and Tissue Engineering: Applications, Trends and Challenges
Authors: Wang Jian , Wang Yurui , Wang Rui , Wang Qiaoli , Wen Min , Wang Jian , Sheng Liyuan , Zheng Yufeng , Xi Tingfei
Published: July 2024

As a 3D rapid prototyping technology, 3D printing (3DP) technology has been widely applied in medical research, fabricating various medical devices or implants. With the development of biomaterials and cell‐related technologies, 3DP, especially bioprinting technology, is quietly bringing great changes and opportunities in the medical industry. Beyond surgical models, medical devices, and implants, traditional 3DP, cell‐based 3D bioprinting, and emerging 4D printing (4DP) have significantly aided in the advancement and manufacture of pharmaceuticals and biological alternatives for tissue engineering. It is envisioned that future healthcare systems, based on evolving 3DP technology and precision medicine, will deliver customized solutions that cater to the unique differences and needs of each patient. In this review work, several mainstream 3D bioprinting technologies are presented, with a focus on recent advances in 3DP for pharmaceutical engineering and important tissue engineering, including vascular and bone tissue engineering. Challenges and future prospects of 3DP for drug discovery, drug delivery systems, artificial blood vessels, vascular and bone tissue engineering scaffolds, and practical applications are also covered. Finally, the differences between 3DP and 4DP, as well as the advantages and disadvantages of different stimulus response mechanisms in 4DP and their potential applications are summarized.
Anti‐CTLA‐4 m2a Antibody Exacerbates Cardiac Injury in Experimental Autoimmune Myocarditis Mice By Promoting Ccl5‐Neutrophil Infiltration
Authors: Wu Ming‐Ming , Yang Yan‐Chao , Cai Yong‐Xu , Jiang Shuai , Xiao Han , Miao Chang , Jin Xi‐Yun , Sun Yu , Bi Xin , Hong Zi , Zhu Di , Yu Miao , Mao Jian‐Jun , Yu Chang‐Jiang , Liang Chen , Tang Liang‐Liang , Wang Qiu‐Shi , Shao Qun , Jiang Qing‐Hua , Pan Zhen‐Wei , Zhang Zhi‐Ren
Published: July 2024

The risk for suffering immune checkpoint inhibitors (ICIs)‐associated myocarditis increases in patients with pre‐existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single‐cell RNA sequencing, and flow cytometry are used to decipher how anti‐cytotoxic T lymphocyte antigen‐4 m2a antibody (anti‐CTLA‐4 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti‐CTLA‐4 m2a antibody increases cardiac fibroblast‐derived C‐X‐C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1‐Cxcr2 chemotaxis. It is identified that the C–C motif chemokine ligand 5 (Ccl5)‐neutrophil subpopulation is responsible for high activity of cytokine production, adaptive immune response, NF‐κB signaling, and cellular response to interferon‐gamma and that the Ccl5‐neutrophil subpopulation and its‐associated proinflammatory cytokines/chemokines promoted macrophage (Mφ) polarization to M1 Mφ. These altered infiltrating landscape and phenotypic switch of immune cells, and proinflammatory factors synergistically aggravated anti‐CTLA‐4 m2a antibody‐induced cardiac injury in EAM mice. Neutralizing neutrophils, Cxcl1, and applying Cxcr2 antagonist dramatically alleviates anti‐CTLA‐4 m2a antibody‐induced leukocyte infiltration, cardiac fibrosis, and dysfunction. It is suggested that Ccl5‐neutrophil subpopulation plays a critical role in aggravating anti‐CTLA‐4 m2a antibody‐induced cardiac injury in EAM mice. This data may provide a strategic rational for preventing/curing ICIs‐associated myocarditis.
Automatic Clinical Assessment of Swallowing Behavior and Diagnosis of Silent Aspiration Using Wireless Multimodal Wearable Electronics
Authors: Shin Beomjune , Lee Sung Hoon , Kwon Kangkyu , Lee Yoon Jae , Crispe Nikita , Ahn So‐Young , Shelly Sandeep , Sundholm Nathaniel , Tkaczuk Andrew , Yeo Min‐Kyung , Choo Hyojung J. , Yeo Woon‐Hong
Published: July 2024

Dysphagia is more common in conditions such as stroke, Parkinson's disease, and head and neck cancer. This can lead to pneumonia, choking, malnutrition, and dehydration. Currently, the diagnostic gold standard uses radiologic imaging, the videofluoroscopic swallow study (VFSS); however, it is expensive and necessitates specialized facilities and trained personnel. Although several devices attempt to address the limitations, none offer the clinical‐grade quality and accuracy of the VFSS. Here, this study reports a wireless multimodal wearable system with machine learning for automatic, accurate clinical assessment of swallowing behavior and diagnosis of silent aspirations from dysphagia patients. The device includes a kirigami‐structured electrode that suppresses changes in skin contact impedance caused by movements and a microphone with a gel layer that effectively blocks external noise for measuring high‐quality electromyograms and swallowing sounds. The deep learning algorithm offers the classification of swallowing patterns while diagnosing silent aspirations, with an accuracy of 89.47%. The demonstration with post‐stroke patients captures the system's significance in measuring multiple physiological signals in real‐time for detecting swallowing disorders, validated by comparing them with the VFSS. The multimodal electronics can ensure a promising future for dysphagia healthcare and rehabilitation therapy, providing an accurate, non‐invasive alternative for monitoring swallowing and aspiration events.
Mass transfer of gas–liquid two‐phase flow in asymmetric parallel microchannels with liquid feed splitting
Authors: Huang Zien , Xiang Xingyu , Jiang Bin , Zhu Chunying , Cui Xianbao , Ma Youguang , Fu Taotao
Published: July 2024

Due to size limitations, the gas–liquid absorption capacity of a single microchannel is limited, making it difficult to achieve large‐scale CO2 capture. Therefore, the parallel microchannels combining the advantages of high efficiency and large throughput stand out. However, when the operating condition is high gas–liquid flow rate ratio, the liquid phase between bubbles almost disappears after multiple distributions, which affects the amount of gas–liquid absorption. In this study, the numbering‐up of the asymmetric parallel microchannels in the gas–liquid absorption process was investigated by splitting the liquid feed stream in two. The flow patterns under different operating conditions were obtained. The flow and distribution of gas–liquid two‐phase flow were investigated, and the reason of the distribution deterioration caused by appearance of long slug bubbles was explained by the pressure drop distribution. The total liquid mass transfer coefficient and bubble residence time were derived and obtained, and the mass transfer was further discussed.
Phenylboronic Acid‐Functionalized Hyaluronic Acid as Polysaccharide Carriers for Diol‐Containing Drugs Delivery
Authors: Zhang Yu‐Hui , Tian Ye , Wang Bo , Cheng Xin‐He , Wang Jie , Xin Siqintana , Sheng Xianliang
Published: July 2024

Packaging hydrophobic drugs into polysaccharide carriers can improve their aqueous solubility, biocompatibility, tumor‐specific accumulation, and therapeutic effect. In this work, phenylboronic acid (PBA) was anchored onto the chain of biocompatible polysaccharide hyaluronic acid (HA) by an amide condensation reaction, which could be used to fabricate stimuli‐responsive targeted drug delivery systems. A series of pH‐responsive conjugated hyaluronic acid nanoparticles composed of a hydrophobic drug core and hydrophilic hyaluronic acid shell were prepared by the boronate‐crosslink of the PBA with diol‐containing anticancer drugs such as capecitabine (CAPE) and aloin (Al). Satisfactory targeted drug release behavior at acidic pH, lower cytotoxicity, and higher anticancer effect were realized by using this polysaccharide carrier. It is believed that this strategy has great potential for polysaccharide modification and anticancer‐associated applications.
Heterozygous Variants in KCNJ10 Cause Paroxysmal Kinesigenic Dyskinesia Via Haploinsufficiency
Authors: Li Yun‐Lu , Lin Jingjing , Huang Xuejing , Zeng Rui‐Huang , Zhang Guangyu , Xu Jie‐Ni , Lin Kai‐Jun , Chen Xin‐Shuo , He Ming‐Feng , Qiao Jing‐Da , Cheng Xuewen , Zhu Dengna , Xiong Zhi‐Qi , Chen Wan‐Jin
Published: July 2024

Objective

Most paroxysmal kinesigenic dyskinesia (PKD) cases are hereditary, yet approximately 60% of patients remain genetically undiagnosed. We undertook the present study to uncover the genetic basis for undiagnosed PKD patients.

Methods

Whole‐exome sequencing was performed for 106 PRRT2‐negative PKD probands. The functional impact of the genetic variants was investigated in HEK293T cells and Drosophila.

Results

Heterozygous variants in KCNJ10 were identified in 11 individuals from 8 unrelated families, which accounted for 7.5% (8/106) of the PRRT2‐negative probands. Both co‐segregation of the identified variants and the significantly higher frequency of rare KCNJ10 variants in PKD cases supported impacts from the detected KCNJ10 heterozygous variants on PKD pathogenesis. Moreover, a KCNJ10 mutation‐carrying father from a typical EAST/SeSAME family was identified as a PKD patient. All patients manifested dystonia attacks triggered by sudden movement with a short episodic duration. Patch‐clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient‐derived variants, indicating a loss‐of‐function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock‐in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia‐specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes.

Interpretation

Our study established haploinsufficiency resulting from heterozygous variants in KCNJ10 can be understood as a previously unrecognized genetic cause for PKD and provided evidence of glial involvement in the pathophysiology of PKD. ANN NEUROL 2024;96:758–773
Ligand‐Controlled Copper‐Catalyzed Halo‐Halodifluoromethylation of Alkenes and Alkynes Using Fluorinated Carboxylic Anhydrides
Authors: Mukherjee Subrata , Aoki Yuma , Kawamura Shintaro , Sodeoka Mikiko
Published: July 2024

Polyhalogenated molecules are often found as bioactive compounds in nature and are used as synthetic building blocks. Fluoroalkyl compounds hold promise for the development of novel pharmaceuticals and agrochemicals, as the introduction of fluoroalkyl groups is known to improve lipophilicity, membrane permeability, and metabolic stability. Three‐component 1,2‐halo‐halodifluoromethylation reactions of alkenes are useful for their synthesis. However, general methods enabling the introduction of halodifluoromethyl (CF2X) and halogen (X’) groups in the desired combination of X and X’ are lacking. To address this gap, for the first time, we report a three‐component halo‐halodifluoromethylation of alkenes and alkynes using combinations of commercially available fluorinated carboxylic anhydrides ((CF2XCO)2O, X=Cl and Br) and alkali metal halides (X’=Cl and Br). In situ prepared fluorinated diacyl peroxides were identified as important intermediates, and the use of appropriate bipyridyl‐based ligands and a copper catalyst was essential for achieving high product selectivity. The synthetic utility of the polyhalogenated products was demonstrated by exploiting differences in the reactivities of their C−X and C−X’ bonds to achieve selective derivatization. Finally, the reaction mechanism and ligand effect were investigated using experimental and theoretical methods to provide important insights for the further development of catalytic reactions.
α’‐Selective Selenium‐catalyzed Allylic C−H Amination of Enol Derivatives
Authors: Dohoda Alexander F. , Rishwain Nicole , Tran Y‐Nhi , Michael Forrest E.
Published: July 2024

A transition metal‐free Se‐catalyzed C−H amination protocol for α’‐amination of enol derivatives has been developed. This reaction can be used to functionalize a wide variety of oxygen‐ and halogen‐substituted alkenes spanning a vast range of nucleophilicities, giving α’‐aminated enol derivatives with high regioselectivity. Amination of E/Z mixtures of alkenes proceeds stereoconvergently to give the (Z)‐enol derivatives exclusively. Mechanistic studies revealed that the relative reactivity and α’‐regioselectivity of these transformations is determined by substantial resonance donation to the heteroatom‐bound carbon in the transition state. These products participate in traditional reactions of enol derivatives, allowing for efficient functionalization of both α‐ and α’‐positions from a single enol derivative with high diastereocontrol.
Stereoselective C−B and C−H Bonds Functionalization of PolyBorylated Alkenes
Authors: Vaishanv Narendra K. , Eghbarieh Nadim , Jagtap Rahul A. , Gose Anthony E. , Haines Brandon E. , Masarwa Ahmad
Published: July 2024

Alkenes are fundamental functional groups which feature in various materials and bioactive molecules; however, efficient divergent strategies for their stereodefined synthesis are difficult. In this regard, numerous synthetic methodologies have been developed to construct carbon–carbon bonds with regio‐ and stereoselectivity, enabling the predictable and efficient synthesis of stereodefined alkenes. In fact, an appealing alternative approach for accessing challenging stereodefined alkene molecular frameworks could involve the sequential selective activation and cross‐coupling of strong bonds instead of conventional C−C bond formation. In this study, we introduce a series of programmed site‐ and stereoselective strategies that capitalizes on the versatile reactivity of readily accessible polymetalloid alkenes (i.e. polyborylated alkenes), through a tandem cross‐coupling reaction, which is catalyzed by an organometallic Rh‐complex to produce complex molecular scaffolds. By merging selective C−B and remote C−H bond functionalization, we achieve the in situ generation of polyfunctional C(sp2)‐nucleophilic intermediates. These species can be further modified by selective coupling reactions with various C‐based electrophiles, enabling the formation of C(sp2)−C(sp3) bond for the generation of even more complex molecular architectures using the readily available starting polyborylated‐alkenes. Mechanistic and computational studies provide insight into the origins of the stereoselectivities and C−H activation via a 1,4‐Rh migration process.
Dissociative Electron Attachment Dynamics of a Promising Cancer Drug Indicates Its Radiosensitizing Potential
Authors: Izadi Farhad , Luxford Thomas F. M. , Sedmidubská Barbora , Arthur‐Baidoo Eugene , Kočišek Jaroslav , Ončák Milan , Denifl Stephan
Published: July 2024

2‐Bromo‐1‐(3,3‐dinitroazetidin‐1‐yl)ethan‐1‐one (RRx‐001) is a hypoxic cell chemotherapeutics with already demonstrated synergism in combined chemo‐radiation therapy. The interaction of the compound with secondary low‐energy electrons formed in large amounts during the physico‐chemical phase of the irradiation may lead to these synergistic effects. The present study focuses on the first step of RRx‐001 interaction with low‐energy electrons in which a transient anion is formed and fragmented. Combination of two experiments allows us to disentangle the decay of the RRx‐001 anion on different timescales. Sole presence of the electron initiates rapid dissociation of NO2 and HNO2 neutrals while NO2− and Br− anions are produced both directly and via intermediate complexes. Based on our quantum chemical calculations, we propose that bidirectional state switching between π*(NO2) and σ*(C−Br) states explains the experimental spectra. The fast dynamics monitored will impact the condensed phase chemistry of the anion as well.
A Strep‐Tag Imprinted Polymer Platform for Heterogenous Bio(electro)catalysis
Authors: Yarman Aysu , Waffo Armel F. T. , Katz Sagie , Bernitzky Cornelius , Kovács Norbert , Borrero Paloma , Frielingsdorf Stefan , Supala Eszter , Dragelj Jovan , Kurbanoglu Sevinc , Neumann Bettina , Lenz Oliver , Mroginski Maria Andrea , Gyurcsányi Róbert E. , Wollenberger Ulla , Scheller Frieder W. , Caserta Giorgio , Zebger Ingo
Published: July 2024

Molecularly imprinted polymers (MIPs) are artificial receptors equipped with selective recognition sites for target molecules. One of the most promising strategies for protein MIPs relies on the exploitation of short surface‐exposed protein fragments, termed epitopes, as templates to imprint binding sites in a polymer scaffold for a desired protein. However, the lack of high‐resolution structural data of flexible surface‐exposed regions challenges the selection of suitable epitopes. Here, we addressed this drawback by developing a polyscopoletin‐based MIP that recognizes recombinant proteins via imprinting of the widely used Strep‐tag II affinity peptide (Strep‐MIP). Electrochemistry, surface‐sensitive IR spectroscopy, and molecular dynamics simulations were employed to ensure an utmost control of the Strep‐MIP electrosynthesis. The functionality of this novel platform was verified with two Strep‐tagged enzymes: an O2‐tolerant [NiFe]‐hydrogenase, and an alkaline phosphatase. The enzymes preserved their biocatalytic activities after multiple utilization confirming the efficiency of Strep‐MIP as a general biocompatible platform to confine recombinant proteins for exploitation in biotechnology.
Stabilization of Short‐ and Long‐Range Magnetic Ordering through the Cooperative Effect of 1D [CuO4]∞ Chains and [CuO2X2] Quadrilateral in Quasi‐1D Spin‐1/2 Systems
Authors: Guo Ruixin , Si Rutong , Li Zhaoyi , Lin Weijie , Wen Bo , Gebauer Ralph , Guo Shu
Published: July 2024

Quasi‐1D chain antiferromagnets with reduced structural dimensionality are a rich playground for investigating novel quantum phenomena. We report the synthesis, crystal structure, and magnetism of two novel quasi‐1D antiferromagnets, β‐PbCu2(TeO3)2Cl2 (I) and PbCu2(TeO3)2Br2 (II). Their magnetic frameworks are constructed via Cu‐based quasi‐1D [Cu(2)O4]∞ zigzag chains with square‐planar [Cu(1)O2X2] (X=Cl or Br) separated among 1D chains. Specific heat measurements show λ peaks at ~9 K and ~19 K for I and II, respectively. Moreover, both broad maximums (χmax=90 K for I and 80 K for II) and small kinks (TN≈9 K for I and 19 K for II) have been observed in magnetic susceptibility measurements of I and II. Bonner–Fisher model fitting, and theoretical analyses were performed to evaluate the magnetic exchange interactions. Our experimental and theoretical results and structure‐properties relationship analysis reveal the coexistence of short‐ and long‐range magnetic ordering from the cooperative effect of 1D [CuO4]∞ chains and [CuO2X2] quadrilateral.
Highly Reversible Sodium‐ion Storage in A Bifunctional Nanoreactor Based on Single‐atom Mn Supported on N‐doped Carbon over MoS2 Nanosheets
Authors: Sui Simi , Xie Haonan , Chen Biao , Wang Tianshuai , Qi Zijia , Wang Jingyi , Sha Junwei , Liu Enzuo , Zhu Shan , Lei Kaixiang , Zheng Shijian , Zhou Guangmin , He Chunnian , Hu Wenbin , He Fang , Zhao Naiqin
Published: July 2024

Conversion‐type electrode materials have gained massive research attention in sodium‐ion batteries (SIBs), but their limited reversibility hampers practical use. Herein, we report a bifunctional nanoreactor to boost highly reversible sodium‐ion storage, wherein a record‐high reversible degree of 85.65 % is achieved for MoS2 anodes. Composed of nitrogen‐doped carbon‐supported single atom Mn (NC‐SAMn), this bifunctional nanoreactor concurrently confines active materials spatially and catalyzes reaction kinetics. In situ/ex situ characterizations including spectroscopy, microscopy, and electrochemistry, combined with theoretical simulations containing density functional theory and molecular dynamics, confirm that the NC‐SAMn nanoreactors facilitate the electron/ion transfer, promote the distribution and interconnection of discharging products (Na2S/Mo), and reduce the Na2S decomposition barrier. As a result, the nanoreactor‐promoted MoS2 anodes exhibit ultra‐stable cycling with a capacity retention of 99.86 % after 200 cycles in the full cell. This work demonstrates the superiority of bifunctional nanoreactors with two‐dimensional confined and catalytic effects, providing a feasible approach to improve the reversibility for a wide range of conversion‐type electrode materials, thereby enhancing the application potential for long‐cycled SIBs.
Life cycle assessment of Luffa‐reinforced epoxy composites: Untreated versus chemically treated fibers
Authors: Anastasiou Dimitrios E.
Published: July 2024

This research conducts a comprehensive cradle‐to‐gate life cycle assessment, comparing four distinct epoxy composites with each other and with the pure matrix. The composites investigated include epoxy resin reinforced with 25% and 50% untreated Luffa cylindrica fiber mats and 25% and 50% chemically treated Luffa cylindrica mats. The study defines the functional unit concerning the load at the fracture point and explores a real‐world scenario related to a potential industrial installation in southeastern Europe. The assessment utilizes 22 ReCiPe 2016 endpoint indicators to quantify impacts on human health, ecosystems, and resource availability. The findings indicate that the 50% chemically treated Luffa cylindrica‐reinforced epoxy has the least environmental impact, closely followed by the 50% untreated Luffa cylindrica. All four composites exhibit lower impacts than the pure epoxy resin. Notably, the 50% Luffa‐reinforced composites stand out as significantly environmentally favorable due to the substitution of fossil‐derived resin with natural fibers. This study underscores the potential of Luffa cylindrica as a promising and eco‐friendly reinforcement for epoxy composites.
Tribological properties of dimensionally stable and high strength Kevlar polyimide composite aerogels
Authors: Mu Bo , Li Yun'an , Du Kang , Dai Xiaoqin , Tian Li , Guo Junhong , Yang Baoping , Cui Jinfeng , Bao Xuemei
Published: July 2024

Dimensionally stable and high strength Polyimide(PI)/nKevlar composite aerogels are fabricated by the inclusion of nano Kevlar fibers with PI precursor polyamide acid via solution mixing and subsequent vacuum drying. The rigid macromolecular structure of nKevlars and the intermolecular hydrogen bonding result in lower shrinkage/density and larger porosity. The PI/nKevlar composite aerogels demonstrate a 23.4% reduction in the linear shrinkage. Compared with pure polyimide aerogel, the friction coefficient and wear rate of composite aerogel decreased significantly, with the dry friction wear rate of the PI/nKevlar‐1.0 reduced by 34.14% and the friction coefficient of the oil‐containing aerogel reduced by 28.29% ascribing to the increased loading bearing of the composite.
Synthesis of a syringaldehyde derivative to enhance the fire resistance and structural strength of epoxy resin
Authors: Chen Zhengpeng , He Xin , Cao Zhengshuai , Li Yunfan , Chen Denglong , Yang Zhiwang , Lei Ziqiang
Published: July 2024

In light of growing environmental apprehensions, the threat of global warming, and the depletion of oil reserves, it is advisable to opt for bio‐epoxy resins sourced from sustainable materials. In response to these issues, syringaldehyde (SH) flame retardant epoxy resin derivatives have been formulated and synthesized. Initially, SH was reacted with 4, 4‐diaminodiphenylmethane (DDM) to yield an intermediate compound, DDM‐SH. Subsequently, the inherently flame‐retardant curing agent (DDM‐SH‐DOPO) and the bio‐based epoxy monomer (DDM‐SH‐EP) were produced by reacting with DOPO and epichlorohydrin, respectively. These resulting compounds were then integrated into bisphenol A epoxy resin, enhancing its flame retardant and mechanical characteristics. The flammability was assessed through limiting oxygen index (LOI), UL‐94, and cone calorimeter tests. The DDM‐SH‐EP‐20/5 sample exhibits notable improvements. It elevates the LOI to 25.3%, achieving a UL‐94 rating to V‐0 and effectively reducing smoke and heat release from the epoxy resin. The ternary cross‐linking network formed between DGEBA, DDM‐SH‐EP, and DDM‐SH‐DOPO primarily contributes to this mechanical enhancement, DDM‐SH‐EP‐20/5 has excellent overall performance, bending strength and bending modulus are 103% and 108% higher than DGEBA/DDM. This study offers a viable solution for producing flame‐retardant epoxy resin with superior mechanical properties.
A hydrologic and land cover‐based habitat model for use in bog turtle (Glyptemys muhlenbergii) conservation
Authors: Feaga Jeffrey B. , Barron Joseph C. , Brooks George C. , Frimpong Emmanuel A. , Haas Carola A. , Holden Michael T. , Hultin Emma A.
Published: July 2024

The endangered bog turtle (Glyptemys muhlenbergii) exemplifies issues related to rare species conservation; presence surveys have low detection and variables used in habitat models can lack relevance to established biological relationships of the species to its environment. The species' use of groundwater saturated soils and stream networks as core habitat and dispersal corridors has been documented. Less is known about the landscape factors that promote the formation and persistence of wetlands used for core habitat.

A GIS‐based resource selection function was developed to predict bog turtle habitat use. Trained on 1 ha plots centred on occupied sites and pseudo‐absent plots constrained to areas within 56.4 m to stream network centrelines, the model tested the capacity of a topographic wetness index (TWI), stream order and soil, wetland and land cover type to predict the presence of suitable habitat and turtle occupancy. Landscape variables were sampled at 10 m resolution, but variable selection and model performance were analysed at 100 m resolution to maintain a biologically relevant 1 ha habitat scale and accommodate the resolution of other variables.

Suitable habitat and turtle presence were best predicted by intermediate to high values of TWI, land cover with low vegetation height and wetlands, second‐ and third‐order streams and the occurrence of mapped National Wetland Inventory polygons and hydric soils. Very high values of TWI were negatively associated with habitat suitability. The area under the curve of the best model was 0.833.

Suitable habitat was found on 88% of 55 independent sites selected using the model and nine new occupied sites were confirmed. Model error is discussed with consideration of human‐altered drainage networks on the agricultural landscape.