bluuebunny/crossref_metadata_2025 huggingface dataset:
Elucidation of Protonation Cooperativity of a STING‐Activating Polymer
Authors: Wang Maggie , Bennett Zachary T. , Singh Parnavi , Feng Qiang , Wilhelm Jonathan , Huang Gang , Gao Jinming
Published: August 2023

Stimuli‐responsive nanomaterials have the potential to improve the performance and overcome existing barriers of conventional nanotherapeutics. Molecular cooperativity design in stimuli‐responsive nanomedicine can amplify physiological signals, enabling a cooperative response for improved diagnostic and therapeutic precision. Previously, this work reported an ultra‐pH‐sensitive polymer, PEG‐b‐PC7A, that possesses innate immune activating properties by binding to the stimulator of interferon genes (STING) through polyvalent phase condensation. This interaction enhances STING activation and synergizes with the endogenous STING ligand for robust cancer immunotherapy. Despite its successes in innate immune activation, the fundamental physicochemical and pH‐responsive properties of PC7A require further investigation. Here, this study elucidates the protonation cooperativity driven by the phase transition of PC7A copolymer. The highly cooperative system displays an “all‐or‐nothing” proton distribution between highly charged unimer (all) and neutral micelle (nothing) states without gradually protonated intermediates. The binary protonation behavior is further illustrated in pH‐precision‐controlled release of a representative anticancer drug, β‐lapachone, by PC7A micelles over a noncooperative PE5A polymer. Furthermore, the bimodal distribution of protons is represented by a high Hill coefficient (nH > 9), featuring strong positive cooperativity. This study highlights the nanoscale pH cooperativity of an immune activating polymer, providing insights into the physicochemical characterization and design parameters for future nanotherapeutics development.
EGFR‐Induced and c‐Src‐Mediated CD47 Phosphorylation Inhibits TRIM21‐Dependent Polyubiquitylation and Degradation of CD47 to Promote Tumor Immune Evasion
Authors: Du Linyong , Su Zhipeng , Wang Silu , Meng Ying , Xiao Fei , Xu Daqian , Li Xinjian , Qian Xu , Lee Su Bin , Lee Jong‐Ho , Lu Zhimin , Lyu Jianxin
Published: August 2023

Tumor cells often overexpress immune checkpoint proteins, including CD47, for immune evasion. However, whether or how oncogenic activation of receptor tyrosine kinases, which are crucial drivers in tumor development, regulates CD47 expression is unknown. Here, it is demonstrated that epidermal growth factor receptor (EGFR) activation induces CD47 expression by increasing the binding of c‐Src to CD47, leading to c‐Src‐mediated CD47 Y288 phosphorylation. This phosphorylation inhibits the interaction between the ubiquitin E3 ligase TRIM21 and CD47, thereby abrogating TRIM21‐mediated CD47 K99/102 polyubiquitylation and CD47 degradation. Knock‐in expression of CD47 Y288F reduces CD47 expression, increases macrophage phagocytosis of tumor cells, and inhibits brain tumor growth in mice. In contrast, knock‐in expression of CD47 K99/102R elicits the opposite effects compared to CD47 Y288F expression. Importantly, CD47‐SIRPα blockade with an anti‐CD47 antibody treatment significantly enhances EGFR‐targeted cancer therapy. In addition, CD47 expression levels in human glioblastoma (GBM) specimens correlate with EGFR and c‐Src activation and aggravation of human GBM. These findings elucidate a novel mechanism underlying CD47 upregulation in EGFR‐activated tumor cells and underscore the role of the EGFR‐c‐Src‐TRIM21‐CD47 signaling axis in tumor evasion and the potential to improve the current cancer therapy with a combination of CD47 blockade with EGFR‐targeted remedy.
Recent Advances in Flexible Wearable Supercapacitors: Properties, Fabrication, and Applications
Authors: Yan Zhe , Luo Sheji , Li Qi , Wu Zhong‐Shuai , Liu Shengzhong (Frank)
Published: August 2023

A supercapacitor is a potential electrochemical energy storage device with high‐power density (PD) for driving flexible, smart, electronic devices. In particular, flexible supercapacitors (FSCs) have reliable mechanical and electrochemical properties and have become an important part of wearable, smart, electronic devices. It is noteworthy that the flexible electrode, electrolyte, separator and current collector all play key roles in overall FSCs. In this review, the unique mechanical properties, structural designs and fabrication methods of each flexible component are systematically classified, summarized and discussed based on the recent progress of FSCs. Further, the practical applications of FSCs are delineated, and the opportunities and challenges of FSCs in wearable technologies are proposed. The development of high‐performance FSCs will greatly promote electricity storage toward more practical and widely varying fields. However, with the development of portable equipment, simple FSCs cannot satisfy the needs of integrated and intelligent flexible wearable devices for long durations. It is anticipated that the combining an FSC and a flexible power source such as flexible solar cells is an effective strategy to solve this problem. This review also includes some discussions of flexible self‐powered devices.
Stabilizing Non‐Fullerene Organic Photodiodes through Interface Engineering Enabled by a Tin Ion‐Chelated Polymer
Authors: Xiao Jianhua , Wang Yang , Yuan Liu , Long Yin , Jiang Zhi , Liu Qingxia , Gu Deen , Li Weizhi , Tai Huiling , Jiang Yadong
Published: August 2023

The recent emergence of non‐fullerene acceptors (NFAs) has energized the field of organic photodiodes (OPDs) and made major breakthroughs in their critical photoelectric characteristics. Yet, stabilizing inverted NF‐OPDs remains challenging because of the intrinsic degradation induced by improper interfaces. Herein, a tin ion‐chelated polyethyleneimine ethoxylated (denoted as PEIE‐Sn) is proposed as a generic cathode interfacial layer (CIL) of NF‐OPDs. The chelation between tin ions and nitrogen/oxygen atoms in PEIE‐Sn contributes to the interface compatibility with efficient NFAs. The PEIE‐Sn can effectively endow the devices with optimized cascade alignment and reduced interface defects. Consequently, the PEIE‐Sn‐OPD exhibits properties of anti‐environmental interference, suppressed dark current, and accelerated interfacial electron extraction and transmission. As a result, the unencapsulated PEIE‐Sn‐OPD delivers high specific detection and fast response speed and shows only slight attenuation in photoelectric performance after exposure to air, light, and heat. Its superior performance outperforms the incumbent typical counterparts (ZnO, SnO2, and PEIE as the CILs) from metrics of both stability and photoelectric characteristics. This finding suggests a promising strategy for stabilizing NF‐OPDs by designing appropriate interface layers.
Therapeutic strategies in vascular cognitive impairment: A systematic review of population, intervention, comparators, and outcomes
Authors: Masserini Federico , Baso Giacomo , Gendarini Claudia , Pantoni Leonardo
Published: August 2023

Introduction

Vascular cognitive impairment (VCI) is a common and heterogeneous condition, clinically and pathophysiologically, that still lacks approved treatment.

Methods

We reviewed evidence from randomized and non‐randomized clinical trials in VCI to explore whether any therapeutic option warrants further investigation and to assess possible flaws in previous studies.

Results

We identified 118 studies after searching PubMed and Embase, including 19,223 participants and 5 different VCI subtypes. We found 63 different types of intervention (51 pharmacologic, 5 employing physical agent application, 7 rehabilitation approaches) compared with either placebo, best medical treatment, or other interventions. Treatment efficacy was assessed through 125 outcome measures (with a clearly pre‐specified primary outcome in 50.8% of studies).

Discussion

Therapeutic trials in VCI have been heterogeneous in terms of populations, types of interventions, and outcomes. Overall, a lack of clear pathophysiological rationale for tested interventions seems to emerge, together with the need to homogenize trial study design
Uterine rupture successfully treated with a damage‐control strategy of hysterectomy and resuscitative endovascular balloon occlusion of the aorta‐assisted cardiopulmonary resuscitation
Authors: Okamoto Yutaro , Ishida Kenichiro , Matsumura Yosuke , Yoshikawa Yoshiaki , Sogabe Taku , Fujikami Yusuke , Ban Kenji , Tatsumi Keiji , Ohnishi Mitsuo
Published: August 2023

Background

Uterine rupture is a major cause of postpartum hemorrhage (PPH) that requires surgery. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is also helpful for PPH. However, the effectiveness of REBOA in PPH with cardiac arrest is unknown.

Case Presentation

A 40‐year‐old woman developed hemorrhagic shock due to uterine rupture after an induced delivery. She developed cardiac arrest, but was rescued by cardiopulmonary resuscitation (CPR), REBOA, a hysterectomy, and pelvic gauze packing. The hemodynamics were too unstable to move to the operating room. Then we initiated the CPR assisted with REBOA and decided to activate massive transfusion and perform laparotomy in the emergency room. She was finally discharged home without neurological sequelae.

Conclusion

Our damage control strategy, including REBOA‐assisted CPR, contributed to saving the life of a patient with a life‐threatening PPH.
Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged ≥4 to <8 Years) with Duchenne Muscular Dystrophy: 1‐Year Interim Results from Study SRP‐9001‐103 (ENDEAVOR)
Authors: Zaidman Craig M. , Proud Crystal M. , McDonald Craig M. , Lehman Kelly J. , Goedeker Natalie L. , Mason Stefanie , Murphy Alexander P. , Guridi Maitea , Wang Shufang , Reid Carol , Darton Eddie , Wandel Christoph , Lewis Sarah , Malhotra Jyoti , Griffin Danielle A. , Potter Rachael A. , Rodino‐Klapac Louise R. , Mendell Jerry R.
Published: August 2023

Objective

Delandistrogene moxeparvovec is approved in the USA for the treatment of ambulatory patients (4–5 years) with Duchenne muscular dystrophy. ENDEAVOR (SRP‐9001‐103; NCT04626674) is a single‐arm, open‐label study to evaluate delandistrogene moxeparvovec micro‐dystrophin expression, safety, and functional outcomes following administration of commercial process delandistrogene moxeparvovec.

Methods

In cohort 1 of ENDEAVOR (N = 20), eligible ambulatory males, aged ≥4 to <8 years, received a single intravenous infusion of delandistrogene moxeparvovec (1.33 × 1014 vg/kg). The primary endpoint was change from baseline (CFBL) to week 12 in delandistrogene moxeparvovec micro‐dystrophin by western blot. Additional endpoints evaluated included: safety; vector genome copies; CFBL to week 12 in muscle fiber‐localized micro‐dystrophin by immunofluorescence; and functional assessments, including North Star Ambulatory Assessment, with comparison with a propensity score‐weighted external natural history control.

Results

The 1‐year safety profile of commercial process delandistrogene moxeparvovec in ENDEAVOR was consistent with safety data reported in other delandistrogene moxeparvovec trials (NCT03375164 and NCT03769116). Delandistrogene moxeparvovec micro‐dystrophin expression was robust, with sarcolemmal localization at week 12; mean (SD) CFBL in western blot, 54.2% (42.6); p < 0.0001. At 1 year, patients demonstrated stabilized or improved North Star Ambulatory Assessment total scores; mean (SD) CFBL, +4.0 (3.5). Treatment versus a propensity score‐weighted external natural history control demonstrated a statistically significant difference in least squares mean (standard error) CFBL in North Star Ambulatory Assessment, +3.2 (0.6) points; p < 0.0001.

Interpretation

Results confirm efficient transduction of muscle by delandistrogene moxeparvovec. One‐year post‐treatment, delandistrogene moxeparvovec was well tolerated, and demonstrated stabilized or improved motor function, suggesting a clinical benefit for patients with Duchenne muscular dystrophy. ANN NEUROL 2023;94:955–968
Reply to Correspondence on “Structural Insight into the Catalytic Mechanism of the Endoperoxide Synthase FtmOx1′′
Authors: Wu Lian , Wang Zhanfeng , Cen Yixin , Wang Binju , Zhou Jiahai
Published: August 2023

The high‐resolution X‐ray crystal structure of the ternary complex FtmOx1 ⋅ 2OG ⋅ fumitremorgin B and the catalytic mechanism were recently reported by us (DOI 10.1002/anie.202112063). In their Correspondence, Zhang, Costello, Liu et al. criticize our work in several aspects. Herein, we address these questions one by one. These structural clarifications and new computational results further support the CarC‐like mechanistic model.
Two‐Second‐Annealed 2D/3D Perovskite Films with Graded Energy Funnels and Toughened Heterointerfaces for Efficient and Durable Solar Cells
Authors: Chang Xueqing , Zhong Jun‐Xing , Li Sibo , Yao Qin , Fang Yuxuan , Yang Guo , Tan Ying , Xue Qifan , Qiu Longbin , Wang Qingqian , Peng Yong , Wu Wu‐Qiang
Published: August 2023

The 2D/3D perovskite heterostructures have been widely investigated to enhance the efficiency and stability of perovskite solar cells (PSCs). However, rational manipulation of phase distribution and energy level alignment in such 2D/3D perovskite hybrids are still of great challenge. Herein, we successfully achieved spontaneous phase alignment of 2D/3D perovskite heterostructures by concurrently introducing both 2D perovskite component and organic halide additive. The graded phase distribution of 2D perovskites with different n values and 3D perovskites induced favorable energy band alignment across the perovskite film and boosted the charge transfer at the relevant heterointerfaces. Moreover, the 2D perovskite component also acted as a “band‐aid” to simultaneously passivate the defects and release the residual tensile stress of perovskite films. Encouragingly, the blade‐coated PSCs based on only ≈2 s in‐situ fast annealed 2D/3D perovskite films with favorable energy funnels and toughened heterointerfaces achieved promising efficiencies of 22.5 %, accompanied by extended lifespan. To our knowledge, this is the highest reported efficiency for the PSCs fabricated with energy‐saved thermal treatment just within a few seconds, which also outperformed those state‐of‐the‐art annealing‐free analogues. Such a two‐second‐in‐situ‐annealing technique could save the energy cost by up to 99.6 % during device fabrication, which will grant its low‐coast implementation.
Regulating the Sequence Structure of Conjugated Block Copolymers Enables Large‐Area Single‐Component Organic Solar Cells with High Efficiency and Stability
Authors: Cheng Yujun , Mao Qilong , Zhou Chunxiang , Huang Xuexiang , Liu Jiabin , Deng Jiawei , Sun Zhe , Jeong Seonghun , Cho Yongjoon , Zhang Youhui , Huang Bin , Wu Feiyan , Yang Changduk , Chen Lie
Published: August 2023

Single‐component organic solar cells (SCOSCs) based on conjugated block copolymers (CBCs) by covalently bonding a polymer donor and polymer acceptor become more and more appealing due to the formation of a favorable and stable morphology. Unfortunately, a deep understanding of the effect of the assembly behavior caused by the sequence structure of CBCs on the device performance is still missing. Herein, from the aspect of manipulating the sequence length and distribution regularity of CBCs, we synthesized a series of new CBCs, namely D18(20)‐b‐PYIT, D18(40)‐b‐PYIT and D18(60)‐b‐PYIT by two‐pot polymerization, and D18(40)‐b‐PYIT(r) by traditional one‐pot method. It is observed that precise manipulation of sequence length and distribution regularity of the polymer blocks fine‐tunes the self‐assembly of the CBCs, optimizes film morphology, improves optoelectronic properties, and reduces energy loss, leading to simultaneously improved efficiency and stability. Among these CBCs, the D18(40)‐b‐PYIT‐based device achieves a high efficiency of 13.4 % with enhanced stability, which is an outstanding performance among SCOSCs. Importantly, the regular sequence distribution and suitable sequence length of the CBCs enable a facile film‐forming process of the printed device. For the first time, the blade‐coated large‐area rigid/flexible SCOSCs are fabricated, delivering an impressive efficiency of 11.62 %/10.73 %, much higher than their corresponding binary devices.
A pilot trial of consolidation bevacizumab after hypo‐fractionated concurrent chemoradiotherapy in patients with unresectable locally advanced non‐squamous non‐small‐cell lung cancer
Authors: Huo LanQing , Chu Chu , Jiang XiaoBo , Zheng ShiYang , Zhang PengXin , Zhou Rui , Chen NaiBin , Guo JinYu , Qiu Bo , Liu Hui
Published: August 2023

Purpose

To determine the feasibility of incorporating bevacizumab consolidation into hypo‐fractionated concurrent chemoradiotherapy (hypo‐CCRT) for patients with unresectable locally advanced non‐squamous non‐small‐cell lung cancer (LA‐NS‐NSCLC).

Patients and Methods

Eligible patients were treated with hypo‐RT (40Gy in 10 fractions) followed by hypo‐boost (24‐28Gy in 6–7 fractions), along with concurrent weekly chemotherapy. Patients who completed the hypo‐CCRT without experiencing ≥G2 toxicities received consolidation bevacizumab every 3 weeks for up to 1 year, until disease progression or unacceptable treatment‐related toxicities.

The primary endpoint was the risk of G4 or higher hemorrhage. Secondary endpoints included progression‐free survival (PFS), overall survival (OS), locoregional failure‐free survival (LRFS), distant metastasis‐free survival (DMFS), and objective response rate (ORR). All time‐to‐event endpoints (OS, PFS, LRFS, and DMFS) were measured from the start of radiotherapy.

Results

Between December 2017 and July 2020, a total of 27 patients were included in the analysis, with a median follow‐up duration of 28.0 months. One patient (3.7%) developed G5 hemorrhage during bevacizumab consolidation. Additionally, seven patients (25.9%) had G3 cough and three patients (11.1%) experienced G3 pneumonitis. The ORR for the entire cohort was 92.6%. The median OS was 37.0 months (95% confidence interval, 8.9–65.1 months), the median PFS was 16.0 months (95% confidence interval, 14.0–18.0 months), the median LRFS was not reached, and the median DMFS was 18.0 months.

Conclusions

This pilot study met its goal of demonstrating the tolerability of consolidation bevacizumab after hypo‐CCRT. Further investigation of antiangiogenic and immunotherapy combinations in LA‐NSCLC is warranted, while the potential for grade 3 respiratory toxicities should be taken into consideration.
Diarylidene‐N‐Methyl‐4‐Piperidones and Spirobibenzopyrans as Antioxidant and Anti‐Inflammatory Agents
Authors: Kumar Rokkam Siva , Mas‐Rosario Javier A. , Joshi Bishnu P. , Joshi Mayank , Choudhury Angshuman Roy , Kar Swayamsiddha , Golakoti Nageswara Rao , Farkas Michelle E.
Published: August 2023

Curcumin has antioxidant properties resulting from its radical scavenging ability and inhibition of inflammation‐associated factors. However, its lack of solubility, instability, and poor bioavailability are impediments to its therapeutic use. As potential alternatives, we synthesized and performed chemical analysis of thirty diarylidene‐N‐methyl‐4‐piperidone (DANMP), diheteroarylidene‐N‐methyl‐4‐piperidone (DHANMP), and spirobibenzopyran (SBP) derivatives, one of which was also characterized by single crystal X‐ray diffraction. All compounds were evaluated for antioxidant activity via 2,2‐Diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging assay and for drug‐like properties in silico. A subset of five compounds was investigated in terms of aqueous solubilities, which were significantly improved compared to that of curcumin. In vitro assessments of cellular and anti‐inflammatory effects were conducted via real time polymerase chain reaction (RT‐PCR) and Griess assays to evaluate the presence of inflammatory/activated (M1) markers and production of nitric oxide (NO) species, which are associated with inflammation. The five compounds reduced levels of markers and NO to extents similar to or better than curcumin in inflamed cells, and showed no adverse effects on cell viability. We show that these compounds possess anti‐inflammatory properties and may be used as curcumin‐substitutes with improved characteristics.
Extraction and Purification, Structural Characterization and Biological Activity of a Polysaccharide, PRP‐1, from Plumeria rubra
Authors: Yu Yongshi , Xia Yingchi , Sun Ningyun , Tian Yamei , Chen Xin , Fan Lixia , Zhao Chaochao , Xia Chenglai , Yang Anping , Liu Hui
Published: August 2023

Polysaccharides derived from the flowers of Plumeria rubra (PRP) have shown a variety of beneficial effects on improving human health. However, the structural features and bioactivities of PRP remain unclear. A novel neutral polysaccharide (named PRP‐1) with a molecular weight of 23 kDa was extracted and purified from the flowers of P. rubra. PRP‐1 was consisted of arabinose, galactose, glucose, xylose and mannose, with a molar ratio of 1.49: 27.89: 50.24: 13.02: 7.36. The structural characterization based on the methylation and 1D/2D nuclear magnetic resonance analyses indicated that PRP‐1 was composed of →4)‐Glcp‐(1→, →4,6)‐Glcp‐(1→, →4)‐Galp‐(1→, →2)‐Galp‐(1→, t‐Gal(p), →4)‐Manp‐(1→, →4,6)‐Manp‐(1→, t‐Man(p), →2)‐Xylp‐(1→, and t‐Xyl(p). Scanning electron microscopy revealed that PRP‐1 possess a compact three‐dimensional curling network structure in the terms of morphology. PRP‐1 exhibited anti‐inflammatory activity, which have moderate inhibitory effects on TNF‐α and IL‐6 production in lipopolysaccharide (LPS)‐induced RAW 264.7 cells. In addition, PRP‐1 showed ABTS, OH radicals scavenging and the Fe2+ chelating effects in a concentration dependent manner. In α‐glucosidase inhibition assay, PRP‐1 did not exhibit inhibitory activity. Overall, these results provide a scientific basis for the utilization of the flowers of P. rubra as a potential functional food ingredient.
Improving the Antibiofouling and Operational Properties of PVDF Membranes Using Synthesized Cu‐SiO2 Nanoparticles in a Submerged Membrane Bioreactor
Authors: Amani Sanaz , Nourizadeh Kazerouni Haleh , Mikaeili Khiavi Shakiba , Akbari Ali , Yegani Reza
Published: August 2023

The effects of synthesized hydrophilic Cu‐SiO2 nanoparticles on the morphology and antibiofouling performance of polyvinylidene fluoride (PVDF) membranes in a membrane bioreactor system were examined. As a result, the pure water flux of the PVDF membrane increased from 47.61 to 71.93 L m−2h−1 in the presence of 1.0 wt % Cu‐SiO2 nanoparticles. Also, the better‐developed finger‐like bulk pores and thicker sponge‐like surface pores for the nanocomposite membranes confirmed the lower phase inversion rate. The total fouling ratio of the membranes was reduced from 53.79 % to 24.13 % in the presence of 1.0 wt % Cu‐SiO2 nanoparticles, while the flux recovery ratio increased from 54.61 % to 88.73 %. In addition, extracellular polymeric substances analysis showed lower protein and carbohydrate formed on the membrane surface for the nanocomposite membranes.
Methodology adjusting for least squares regression slope in the application of multiplicative scatter correction to near‐infrared spectra of forage feed samples
Authors: Dhanoa Mewa S. , López Secundino , Sanderson Ruth , Lister Sue J. , Barnes Ralph J. , Ellis Jennifer L. , France James
Published: August 2023

Scatter corrections are commonly applied to refine near‐infrared (NIR) spectra. The aim of this study is to assess the impact of measurement errors when using ordinary least squares (OLS) for multiplicative scatter correction (MSC). Any measurement errors attached to the set‐mean spectrum may attenuate the OLS slope and that in turn will affect the estimate of the intercept and the adjustment of the spectra when using MSC methods to mitigate scattering. A corrected least squares slope may be used instead to prevent this problem, although the impact of this approach on the final outcome will depend on the relative size of the measurement errors in the individual spectra and the set‐mean spectrum. The errors‐in‐variables or type II regression model (also known as Deming regression) and its special cases, major axis (MA) and reduced major axis (RMA), are discussed and illustrated. The extent of OLS slope bias or attenuation is demonstrated as is the resulting MSC spectral distortion. Further modification to the MSC transformation method is also suggested. The influence of scattering correction (by MSC, standard normal variate (SNV) and detrending) and of using the maximum likelihood estimate of the slope for MSC on the prediction of chemical composition of Lucerne herbage from NIR spectra was assessed. The predictive performance was slightly improved by the use of scattering corrections with fairly minor differences among methods. Nonetheless, it seems well worth considering the use of type II regression models for assessing MSC application aiming at improving the goodness of prediction from NIR spectra.
Direct Solution‐Phase Synthesis and Functionalization of 2D WSe2 for Ambient Stability
Authors: Sasikala Suchithra Padmajan , Prabhakaran Prem , Baskaran Sambath , Kim Jun Tae , Lee Gang San , Yoon Yeo Hoon , Choi Hee Jae , Kim Jin Goo , Kim Jun Beom , Kim Sang Ouk
Published: August 2023

2H phase tungsten diselenide (WSe2) is a p‐type 2D semiconductor from the transition metal dichalcogenides (TMDs) family with unique optoelectrical properties. Solution phase production of atomically thin WSe2 is challenging due to its instability under ambient conditions. We present a highly efficient and scalable solution method for simultaneously exfoliating and functionalizing WSe2 by leveraging the non‐covalent interaction between mercapto‐group and bulk WSe2. Single and few‐layer 2H phase pure WSe2 sheets of lateral size up to 5 μm with minimal basal plane defects, as revealed by XPS, Raman and FTIR spectroscopy, are produced in a water‐ethanol mixture. Remarkably, WSe2 dispersion remains stable even at high concentrations (10 mg/mL) and exhibited high colloidal stability with a shelf‐life exceeding a year. The findings from our study suggest that through precise manipulation of intercalation chemistry, mass production of solution‐processable phase‐sensitive 2D materials such as WSe2 can be achieved. This advancement holds great potential for facilitating their practical utilization in various real‐world applications.
In silico Investigation of the Thermochemistry and Photoactivity of Pyruvic Acid in an Aqueous Solution of NaCl
Authors: Pollet Rodolphe , Chin Wutharath
Published: August 2023

The photochemistry of oxocarboxylic acids contributes significantly to the complex chemistry occurring in the atmosphere. In this regard, pyruvic acid undergoes photoreactions that lead to many diverse products. The presence of sodium cation near pyruvic acid in an aqueous solution, or its conjugate base in non‐acidic conditions, influences the hydration equilibrium and the photosensitivity to UV‐visible light of the oxocarboxylic acid. We performed an ab initio metadynamics simulation which serves two purposes: first, it unveils the mechanisms of the reversible hydration reaction between the keto and the diol forms, with a free‐energy difference of only 2 kJ/mol at 300 K, which shows the influence of sodium on the keto/diol ratio; second, it provides solvent‐shared ion pairing (SSIP) and contact ion pairing (CIP) structures, including Na+ coordinated to carbonyl, for the calculations of the electronic transition energies to an antibonding π* orbital, which sheds light on the photoactivity of these two forms in the actinic region.
UPDATED PROTOCOL: Universal school‐based programmes for improving social and emotional outcomes in children aged 3–11 years: An evidence and gap map
Authors: Hanratty Jennifer , Miller Sarah , Rodriguez Leonor , Connolly Paul , Roberts Jennifer , Sloan Seaneen , Brennan‐Wilson Aoibheann , Bradshaw Daragh , Coughlan Christopher , Gleghorne Nicole , Dunne Laura , Millen Sharon , Smith Aimee , O'Sullivan Cadhla
Published: August 2023

This is the protocol for an evidence and gap map. The objective of this EGM is to identify and map all primary studies (including randomised and cluster randomised trials) and systematic reviews on universal, school‐based social and emotional learning programmes for young children (3–11 years) to create a live, searchable, and publicly available evidence and gap map.
Low TP53 variant allele frequency as a biomarker for anti‐programmed death (ligand) 1 monotherapy in lung adenocarcinoma
Authors: Wang Shouzheng , Xie Tongji , Li Yan , Guo Lei , Ying Jianming , Wang Yan , Hao Xuezhi , Wang Xingyuan , Li Junling , Xing Puyuan
Published: August 2023

Background

TP53 mutation heterogeneity should be considered when using TP53 as a predictive biomarker for anti–programmed death (ligand) 1 (PD‐(L)1) monotherapy in lung adenocarcinoma (LUAD). However, whether TP53 variant allele frequency (VAF) should also be considered remains unknown.

Methods

Patients with LUAD from both published research and the local cohort were included to discover and validate the relationship between TP53 VAF and the efficacy of PD‐(L)1 inhibitors. The Cancer Genome Atlas (TCGA) LUAD data were included for genomic, transcriptomic, and tumor microenvironment analysis.

Results

Among 159 patients in the discovery cohort, low TP53 VAF patients (VAF ≤ 25%) experienced significantly longer progression‐free survival (PFS) than both high TP53 VAF (5.4 vs. 3.3 months; p = .021) and TP53‐wild‐type patients (5.4 vs. 2.5 months; p = .011). Multivariate Cox regression revealed low TP53 VAF as an independent biomarker of better efficacy. Among 50 patients in the combined validation cohort, median PFS of low TP53 VAF patients was also significantly longer than that of high TP53 VAF patients (12.0 vs. 2.1 months; p = .037). Analyzed with 469 TCGA LUAD samples, low TP53 VAF is associated with significantly higher PD‐L1 expression, enrichment of gene sets related to T‐cell activation, T cell–mediated immunity, and interferon‐γ signaling pathways, and independently associated with more tumor‐infiltrating CD8+ T cells compared with both high TP53 VAF and TP53‐wild type.

Conclusions

TP53 VAF should also be considered when using TP53 as a predictive biomarker. Only low TP53 VAF is independently associated with better efficacy of anti–PD‐(L)1 monotherapy, which may result from higher PD‐L1 expression and more tumor‐infiltrating CD8+ T cells.
Computational Insights on the Hydride and Proton Transfer Mechanisms of D‐Arginine Dehydrogenase
Authors: Yildiz Ibrahim
Published: August 2023

D‐Arginine dehydrogenase from Pseudomonas aeruginosa (PaDADH) is an amine oxidase which catalyzes the conversion of D‐arginine into iminoarginine. It contains a non‐covalent FAD cofactor that is involved in the oxidation mechanism. Based on substrate, solvent, and multiple kinetic isotope effects studies, a stepwise hydride transfer mechanism is proposed. It was shown that D‐arginine binds to the active site of enzyme as α‐amino group protonated, and it is deprotonated before a hydride ion is transferred from its α‐C to FAD. Based on a mutagenesis study, it was concluded that a water molecule is the most likely catalytic base responsible from the deprotonation of α‐amino group. In this study, we formulated computational models based on ONIOM method to elucidate the oxidation mechanism of D‐arginine into iminoarginine using the crystal structure of enzyme complexed with iminoarginine. The calculations showed that Arg222, Arg305, Tyr249, Glu87, His 48, and two active site water molecules play key roles in binding and catalysis. Model systems showed that the deprotonation step occurs prior to hydride transfer step, and active site water molecule(s) may have participated in the deprotonation process.
Scarless Modification of the Drosophila Genome Near Any Mapped attP Sites
Authors: Feng Siqian , Mann Richard S.
Published: August 2023

Here we describe a Drosophila genome engineering technique that can scarlessly modify genomic sequences near any mapped attP attachment site previously integrated by transposon mobilization or gene targeting. This technique combines two highly efficient and robust procedures: phiC31 integrase–mediated site‐specific integration and homing endonuclease–mediated resolution of local duplications. In this technique, a donor fragment containing the desired mutation(s) is first integrated into a selected attP site near the target locus by phiC31 integrase–mediated site‐specific integration, which creates local duplications consisting of the mutant‐containing donor fragment and the wild‐type target locus. Next, homing endonuclease–induced double‐stranded DNA breaks trigger recombination between the duplications and resolve the target locus to generate scarless mutant alleles. In every step, the desired flies can be easily identified by patterns of dominant markers, so no large‐scale screens are needed. This technique is highly efficient and can be used to generate scarless point mutations, insertions, and deletions. The availability of large libraries of mapped attP site–containing transposon/CRISPR insertions in Drosophila allows the modification of more than half of the euchromatic Drosophila genome at a high efficiency. As more and more attP‐containing insertions are generated and mapped, this technique will be able to modify larger portions of the Drosophila genome. The principles of this technique are applicable to other organisms where modifications to the genome are feasible. © 2023 Wiley Periodicals LLC.

Basic Protocol 1: Verifying attP‐containing insertions

Support Protocol: Extracting genomic DNA

Basic Protocol 2: Generating the donor plasmid

Basic Protocol 3: Injecting the donor plasmid and establishing transformant stocks

Basic Protocol 4: Verifying the transformants

Basic Protocol 5: Generating the final scarless alleles

Basic Protocol 6: Verifying the final alleles
A High‐Throughput Absolute Quantification of Protein‐Bound Sulfur Amino Acids from Model and Crop Plant Seeds
Authors: Yobi Abou , Ansaf Huda , Angelovici Ruthie
Published: August 2023

In this procedure, we describe a high‐throughput absolute quantification protocol for the protein‐bound sulfur amino acids, cysteine (Cys) and methionine (Met), from plant seeds. This procedure consists of performic acid oxidation that transforms bound Cys into cysteic acid (CysA) and bound Met into methionine sulfone (MetS) followed by acid hydrolysis. The absolute quantification step is performed by multiple reaction monitoring tandem mass spectrometry (LC‐MS/MS). The approach facilitates the analysis of a few hundred samples per week by using a 96‐well plate extraction setup. Importantly, the method uses only ∼4 mg of tissue per sample and uses the common acid hydrolysis protocol, followed by water extraction that includes DL‐Ser‐d3 and L‐Met‐d3 as internal standards to enable the quantification of the absolute levels of the protein‐bound Cys and Met with high precision, accuracy, and reproducibility. The protocol described herein has been optimized for seed samples from Arabidopsis thaliana, Glycine max, and Zea mays but could be applied to other plant tissues. © 2023 Wiley Periodicals LLC.

Basic Protocol: Analysis of protein‐bound cysteine and methionine from seeds
Use of a hybrid intelligence decision tree to identify mature B‐cell neoplasms
Authors: Vergnolle Inès , Ceccomarini Theo , Canali Alban , Rieu Jean‐Baptiste , Vergez François
Published: August 2023

Background

Mature B‐cell neoplasms are challenging to diagnose due to their heterogeneity and overlapping clinical and biological features. In this study, we present a new workflow strategy that leverages a large amount of flow cytometry data and an artificial intelligence approach to classify these neoplasms.

Methods

By combining mathematical tools, such as classification algorithms and regression tree (CART) models, with biological expertise, we have developed a decision tree that accurately identifies mature B‐cell neoplasms. This includes chronic lymphocytic leukemia (CLL), for which cytometry has been extensively used, as well as other non‐CLL subtypes.

Results

The decision tree is easy to use and proposes a diagnosis and classification of mature B‐cell neoplasms to the users. It can identify the majority of CLL cases using just three markers: CD5, CD43, and CD200.

Conclusion

This approach has the potential to improve the accuracy and efficiency of mature B‐cell neoplasm diagnosis.
Bi‐directional LSTM based channel estimation in 5G massive MIMO OFDM systems over TDL‐C model with Rayleigh fading distribution
Authors: Shankar Ravi
Published: August 2023

In this work, a deep learning (DL)‐based massive multiple‐input multiple‐output (mMIMO) orthogonal frequency division multiplexing (OFDM) system is investigated over the tapped delay line type C (TDL‐C) model with a Rayleigh fading distribution at frequencies ranging from 0.5 to 100 GHz. The proposed bi‐directional long short‐term memory (Bi‐LSTM) channel state information (CSI) estimator uses online learning during training and offline learning during the practical implementation phase. The design of the estimator takes into account situations in which prior knowledge of channel statistics is limited and targets excellent performance, even with limited pilot symbols (PS). Three separate loss functions (mean square logarithmic error [MSLE], Huber, and Kullback–Leibler Distance [KLD]) are assessed in three classification layers. The symbol error rate (SER) and outage probability performance of the proposed estimator are evaluated using a number of optimization techniques, such as stochastic gradient descent (SGD), momentum, and the adaptive gradient (AdaGrad) algorithm. The Bi‐LSTM‐based CSI estimator is trained considering a specific number of PS. It can be readily seen that by incorporating a cyclic prefix (CP), the system becomes more resilient to channel impairments, resulting in a lower SER. Simulations show that the SGD optimization approach and Huber loss function‐trained Bi‐LSTM‐based CSI estimator have the lowest SER and very high estimation accuracy. By using deep neural networks (DNNs), the Bi‐LSTM method for CSI estimation achieves a superior channel capacity (in bps/Hz) at 10 dB than long short‐term memory (LSTM) and other conventional CSI estimators, such as minimum mean square error (MMSE) and least squares (LS). The simulation results validate the analytical results in the study.
Cytological features of chordoid glioma: A case report with summary of prior published cases
Authors: Mohin Md , Ghosh Sudip Kumar , Datta Gitanjali , Chatterjee Uttara
Published: August 2023

Chordoid glioma is an uncommon low‐grade glioma and is a CNS WHO grade 2 tumour in the current WHO 2021 classification. Predominantly it is seen in the third ventricle and in young adults. Although the histological features of chordoid glioma are well documented, there is sparse literature describing its cytological features. Here we describe the squash cytological features of a case of chordoid glioma along with summary of prior published cases. The smears tend to be quite cellular, the cells show mild pleomorphism, anisonucleosis, and absent mitotic activity. The background shows a distinctive bluish myxoid stroma. It can be mistaken for high grade glioma on squash cytology.
Stepping stones to extirpation: Puma patch occupancy thresholds in an urban‐wildland matrix
Authors: Stoner David C. , McDonald Zara , Coon Courtney A. C.
Published: August 2023

Habitat loss and fragmentation are the leading causes of species range contraction and extirpation, worldwide. Factors that predict sensitivity to fragmentation include high trophic level, large body size, and extensive spatial requirements. Pumas (Puma concolor) exemplify these qualities, making them particularly susceptible to fragmentation and subsequent reductions in demographic connectivity. The chaparral‐dominated ecosystems surrounding the greater San Francisco Bay Area encompass over 10,000 km2 of suitable puma habitat, but inland waterways, croplands, urban land uses, and extensive transportation infrastructure have resulted in widespread habitat fragmentation. Pumas in this region now exist as a metapopulation marked by loss of genetic diversity, collisions with vehicles, and extensive human–puma conflict. Given these trends, we conducted a photo survey from 2017 to 2021 across 19 patches of predicted habitat and compiled a dataset of >6584 puma images. We used a logistic regression analytical framework to evaluate the hypothesis that puma patch occupancy would exhibit a threshold response explained by patch size, isolation, and habitat quality. Contrary to predictions, only variables related to patch size demonstrated any power to explain occupancy. On average, occupied patches were 18× larger than those where they were not detected (825 ± 1238 vs. 46 ± 101 km2). Although we observed pumas in patches as small as 1 km2, logistic regression models indicated a threshold occupancy probability between 300 and 400 km2, which is remarkably close to the mean male puma home range size in coastal California (~381 km2). Puma populations dependent on habitats below this value may be susceptible to inbreeding depression and human–wildlife conflict, and therefore vulnerable to extirpation. For species conservation, we suggest conflicts might be ameliorated by identifying the largest, isolated patches for public education campaigns with respect to management of domestic animals, and remaining connective parcels be identified, mapped, and prioritized for targeted mitigation.
Molecular diet analysis of common cranes (Grus grus) under supplementary feeding based on fecal DNA metabarcoding
Authors: Zhao Xinyi , Jiang Haoming , Xu Nan , Zhao Yongqiang , Zhao Fangju , Xu Runfeng , Liu Hongyi
Published: August 2023

The migratory and omnivorous common crane (Grus grus) uses a nature reserve with crucial ecological value that provides supplementary food resources, although the extent of their use by these cranes is unknown. In this study, we used DNA metabarcoding of plants through the chloroplast rbcL gene to investigate the diets of 25 common crane fecal samples and performed analyses in conjunction with supplementary feeding. The results showed that common cranes preferred plants of the families Poaceae and Cyperaceae, similar to common cranes in other nature reserves. Before supplementary feeding, Poaceae and Cyperaceae accounted for 43.83 ± 20.58% and 53.51 ± 19.24%, respectively, while after that, they accounted for 61.23 ± 35.19% and 24.07 ± 28.20%, respectively. The relative abundance of Hordeum increased significantly in January, accounting for 33.88 ± 31.32%, which was mainly affected by supplementary feeding. Therefore, under supplementary feeding, foraging grounds and feeding preferences of common cranes may change correspondingly. The quantity of corn kernels and wheat grains can be increased appropriately in supplementary feeding measures in the nature reserve, and more supplementary feeding sites should be set up in response to the shortage of wild bird food resources. This study applied an effective method to study the diet preference of common cranes under supplementary feeding and further provided insights to improve management measures in the nature reserve.
Snag decomposition following stand‐replacing wildfires alters wildlife habitat use and surface woody fuels through time
Authors: Peterson David W. , Dodson Erich K. , Harrod Richy J.
Published: August 2023

High‐severity wildfires create pulses of snags that serve a variety of functions as they decompose over time. Snag‐related benefits (and hazards) are often linked to specific decomposition stages, but snag decomposition rates and pathways are not well understood in many forest types. We examined temporal patterns of snag decomposition, wildlife cavity creation, and surface woody fuel dynamics in dry coniferous forests of the interior Pacific Northwest region of North America by sampling 159 forest stands within a 39‐year chronosequence of stand‐replacing wildfires in dry coniferous forests dominated by ponderosa pine and Douglas‐fir. We found that most snags broke or fell during the first 15 years after wildfire; small‐diameter snags mostly broke off at or near ground level, while many large‐diameter snags initially broke off above a height of 2 m and then remained standing for an extended period. Ponderosa pine and lodgepole pine snags fell earlier than Douglas‐fir and true fir snags of comparable diameter classes. Wildlife cavities were most common in stands surveyed 8–20 years after fire and in snags with broken tops but were not limited to large diameter snags. Cavity snag diameters ranged from 17 to 98 cm, with 64% of cavity snags having diameters between 30 and 60 cm and 22% of cavity snags having diameters >60 cm. Surface woody fuels increased as snags broke and fell, reaching maximum levels in all size classes 15–20 years after fire. The percentage of large diameter rotten woody fuels increased steadily beginning about 15 years after fire, with implications for fuel management and subsequent wildfire behavior and severity. Our study supports the proposition that fire‐killed snags represent a transient resource pulse in which the relative contribution of snags to different ecological functions varies with snag diameter, species, time since fire, and landscape position.
CD1a and bound lipids drive T‐cell responses in human skin disease
Authors: Ogg Graham S. , Rossjohn Jamie , Clark Rachael A. , Moody D. Branch
Published: August 2023

In addition to serving as the main physical barrier with the outside world, human skin is abundantly infiltrated with resident αβ T cells that respond differently to self, infectious, microbiome, and noxious stimuli.  To study skin T cells during infection and inflammation, experimental biologists track T‐cell surface phenotypes and effector functions, which are often interpreted with the untested assumption that MHC proteins and peptide antigens drive measured responses.  However, a broader perspective is that CD1 proteins also activate human T cells, and in skin, Langerhans cells (LCs) are abundant antigen presenting cells that express extremely high levels of CD1a.  The emergence of new experimental tools, including CD1a tetramers carrying endogenous lipids, now show that CD1a‐reactive T cells comprise a large population of resident T cells in human skin.  Here, we review studies showing that skin‐derived αβ T cells directly recognize CD1a proteins, and certain bound lipids, such as contact dermatitis allergens, trigger T‐cell responses. Other natural skin lipids inhibit CD1a‐mediated T‐cell responses, providing an entry point for the development of therapeutic lipids that block T‐cell responses. Increasing evidence points to a distinct role of CD1a in type 2 and 22 T‐cell responses, providing new insights into psoriasis, contact dermatitis, and other T‐cell‐mediated skin diseases.
Silyl‐ and Germyl‐Substituted Diorganophosphonites
Authors: Hettich Thomas D. , Rudolf Richard , Birchall Nicholas , Nieger Martin , Gudat Dietrich
Published: August 2023

Reactions of metalated diorganophosphonite boranes with triorganosilyl and ‐germyl halides provided borane adducts of diorgano(tetryl)phosphonites. Further treatment with excess Et3N or DABCO yielded the borane‐free species (RO)2P‐ER′3 (E=Si, Ge; R, R′=alkyl, aryl). The products of all reactions were characterized by elemental analyses and NMR data, and in selected cases by MS and single‐crystal XRD studies. Reactions of selected ligands with Ni(CO)4 and selenium were shown to produce Ni(CO)3‐complexes or diorgano(tetryl) phosphonoselenoates (RO)2(R′3E)P=Se, respectively, which were identified spectroscopically but could not be isolated. Evaluation of the TEP and 1JPSe coupling constants were used for a first assessment of the electron donor properties of the new molecules.