bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational modeling and quantitative physiology reveal central parameters for brassinosteroid-regulated early cell physiological processes linked to elongation growth of the Arabidopsis root
Authors: Großeholz Ruth , Wanke Friederike , Rohr Leander , Glöckner Nina , Rausch Luiselotte , Scholl Stefan , Scacchi Emanuele , Spazierer Amelie-Jette , Shabala Lana , Shabala Sergey , Schumacher Karin , Kummer Ursula , Harter Klaus
Published: September 2022

Brassinosteroids (BR) are key hormonal regulators of plant development. However, whereas the individual components of BR perception and signaling are well characterized experimentally, the question of how they can act and whether they are sufficient to carry out the critical function of cellular elongation remains open. Here, we combined computational modeling with quantitative cell physiology to understand the dynamics of the plasma membrane (PM)-localized BR response pathway during the initiation of cellular responses in the epidermis of the Arabidopsis root tip that are be linked to cell elongation. The model, consisting of ordinary differential equations, comprises the BR-induced hyperpolarization of the PM, the acidification of the apoplast and subsequent cell wall swelling. We demonstrate that the competence of the root epidermal cells for the BR response predominantly depends on the amount and activity of H+-ATPases in the PM. The model further predicts that an influx of cations is required to compensate for the shift of positive charges caused by the apoplastic acidification. A potassium channel was subsequently identified and experimentally characterized, fulfilling this function. Thus, we established the landscape of components and parameters for physiological processes potentially linked to cell elongation, a central process in plant development.
Genetically manipulating endogenous Kras levels and oncogenic mutations in vivo influences tissue patterning of murine tumorigenesis
Authors: Le Roux Özgün , Pershing Nicole LK , Kaltenbrun Erin , Newman Nicole J , Everitt Jeffrey I , Baldelli Elisa , Pierobon Mariaelena , Petricoin Emanuel F , Counter Christopher M
Published: September 2022

Despite multiple possible oncogenic mutations in the proto-oncogene KRAS, unique subsets of these mutations are detected in different cancer types. As KRAS mutations occur early, if not being the initiating event, these mutational biases are ostensibly a product of how normal cells respond to the encoded oncoprotein. Oncogenic mutations can impact not only the level of active oncoprotein, but also engagement with proteins. To attempt to separate these two effects, we generated four novel Cre-inducible (LSL) Kras alleles in mice with the biochemically distinct G12D or Q61R mutations and encoded by native (nat) rare or common (com) codons to produce low or high protein levels. While there were similarities, each allele also induced a distinct transcriptional response shortly after activation in vivo. At one end of the spectrum, activating the KrasLSL-natG12D allele induced transcriptional hallmarks suggestive of an expansion of multipotent cells, while at the other end, activating the KrasLSL-comQ61R allele led to hallmarks of hyperproliferation and oncogenic stress. Evidence suggests that these changes may be a product of signaling differences due to increased protein expression as well as the specific mutation. To determine the impact of these distinct responses on RAS mutational patterning in vivo, all four alleles were globally activated, revealing that hematolymphopoietic lesions were permissive to the level of active oncoprotein, squamous tumors were permissive to the G12D mutant, while carcinomas were permissive to both these features. We suggest that different KRAS mutations impart unique signaling properties that are preferentially capable of inducing tumor initiation in a distinct cell-specific manner.
Highly efficient generation of isogenic pluripotent stem cell models using prime editing
Authors: Li Hanqin , Busquets Oriol , Verma Yogendra , Syed Khaja Mohieddin , Kutnowski Nitzan , Pangilinan Gabriella R , Gilbert Luke A , Bateup Helen S , Rio Donald C , Hockemeyer Dirk , Soldner Frank
Published: September 2022

The recent development of prime editing (PE) genome engineering technologies has the potential to significantly simplify the generation of human pluripotent stem cell (hPSC)-based disease models. PE is a multicomponent editing system that uses a Cas9-nickase fused to a reverse transcriptase (nCas9-RT) and an extended PE guide RNA (pegRNA). Once reverse transcribed, the pegRNA extension functions as a repair template to introduce precise designer mutations at the target site. Here, we systematically compared the editing efficiencies of PE to conventional gene editing methods in hPSCs. This analysis revealed that PE is overall more efficient and precise than homology-directed repair of site-specific nuclease-induced double-strand breaks. Specifically, PE is more effective in generating heterozygous editing events to create autosomal dominant disease-associated mutations. By stably integrating the nCas9-RT into hPSCs we achieved editing efficiencies equal to those reported for cancer cells, suggesting that the expression of the PE components, rather than cell-intrinsic features, limit PE in hPSCs. To improve the efficiency of PE in hPSCs, we optimized the delivery modalities for the PE components. Delivery of the nCas9-RT as mRNA combined with synthetically generated, chemically-modified pegRNAs and nicking guide RNAs improved editing efficiencies up to 13-fold compared with transfecting the PE components as plasmids or ribonucleoprotein particles. Finally, we demonstrated that this mRNA-based delivery approach can be used repeatedly to yield editing efficiencies exceeding 60% and to correct or introduce familial mutations causing Parkinson’s disease in hPSCs.
A new imperialist competitive algorithm with spiral rising mechanism for solving path optimization problems
Authors: Li Xia , Chen Junhan , Sun Lingfang , Li Jing
Published: September 2022

Intelligent optimization algorithms have now become important means for solving global optimization problems. The imperialist competitive algorithm (ICA) is a nature-inspired meta-heuristic algorithm that imitates social behavior. ICA has been widely used in optimization problems, however, ICA tends to fall into a local optimal solution because of its fast convergence speed, which may lead to premature convergence when solving optimization problems. To solve these problems, a new improved ICA algorithm is proposed. Based on the original ICA algorithm, the theory of spiral rising is introduced to enlarge the search space and enhance the global search ability of the algorithm based on ensuring the necessary speed of convergence. In this paper, the improved optimization algorithm is applied to 19 classical benchmark functions, and the improved ICA is applied to the robot path optimization problems to solve the optimal path. The improved ICA algorithm improves the optimization ability and algorithm stability.
Prevalence of Third-Party Tracking on Abortion Clinic Web Pages
Authors: Friedman Ari B. , Bauer Lujo , Gonzales Rachel , McCoy Matthew S.
Published: September 2022

This cross-sectional study assesses how often third-party domains use tracking data from visitors to abortion clinic web pages.
Abemaciclib and Fulvestrant for Bilateral Choroidal Metastasis From Breast Carcinoma
Authors: Barke Matthew R. , Agrawal Kushal U. , Shields Carol L.
Published: September 2022

This case report discusses the follow-up of a woman with HR+/ERBB2 invasive ductal breast carcinoma metastatic to the lungs, brain, and spine.
Two‐Step Preaging of an Al–Mg–Si Alloy
Authors: Yang Zi , Cheng Junjie , Liang Zeqin , Banhart John
Published: September 2022

Preaging (PA) is an industrial routine that suppresses the deleterious effect of natural aging and enhances the final paint‐bake hardening of 6XXX aluminum alloys. In view of the different advantages of PA at high and low temperatures, the effects of performing PA in two steps at different temperatures, namely, 80 and 160 °C, are explored. Various two‐step PA combinations are investigated, involving both the temperature orders and various aging times at both temperatures, while aiming at the same hardness after all PA treatments. These results are interpreted on the basis of cluster formation and vacancy evolution during two‐step PA. In particular, the first PA step is found to play a more important role than suggested by the durations of the two PA steps as the clusters formed in the first step can strongly influence the subsequent evolution of both clusters and vacancies in the second step. It is found that two‐step PA results in a compromise between the effects of one‐step PA at both temperatures, that is, the enhancement of natural secondary aging stability is accompanied by a reduced paint‐bake hardening or vice versa.
Wafer‐Scale Radial Junction Solar Cells with 21.1% Efficiency Using c‐Si Microwires
Authors: Choi Deokjae , Hwang Inchan , Lee Youri , Lee Myounghyun , Um Han‐Don , Seo Kwanyong
Published: September 2022

Microwire (MW)‐based radial junction crystalline silicon (c‐Si) solar cells have great potential as an emerging energy device with an efficiency of over 20%. However, the competitive efficiency of MW‐based c‐Si solar cells in realizing a wafer‐scale device is limiting its commercialization. In this study, the aim is to demonstrate that conventional fabrication techniques can be applied to MW‐based solar cells while not only increasing the size from the lab‐scale to the wafer‐scale but also retaining an efficiency of >20%. Surprisingly, an improvement in open‐circuit voltage and fill factor is observed with an increase in device size, due to the reduction of recombination loss at the device edge. Finally, a successful demonstration of 21.1% efficiency at 4‐inch wafer‐scale (25 cm2) in c‐Si MW solar cell is observed, while an efficiency of 20.6% at a lab‐scale size (1 cm2) is observed.
Challenges of Wafer‐Scale Integration of 2D Semiconductors for High‐Performance Transistor Circuits
Authors: Schram Tom , Sutar Surajit , Radu Iuliana , Asselberghs Inge
Published: September 2022

Large‐area 2D‐material‐based devices may find applications as sensor or photonics devices or can be incorporated in the back end of line (BEOL) to provide additional functionality. The introduction of highly scaled 2D‐based circuits for high‐performance logic applications in production is projected to be implemented after the Si‐sheet‐based CFET devices. Here, a view on the requirements needed for full wafer integration of aggressively scaled 2D‐based logic circuits, the status of developments, and the definition of the gaps to be bridged is provided. Today, typical test vehicles for 2D devices are single‐sheet devices fully integrated in a lab environment, but transfer to a more scaled device in a fab environment has been demonstrated. This work reviews the status of the module development, including considerations for setting up fab‐compatible process routes for single‐sheet devices. While further development on key modules is still required, substantial progress is made for MX2 channel growth, high‐k dielectric deposition, and contact engineering. Finally, the process requirements for building ultra‐scaled stacked nanosheets are also reflected on.
Design, Development, and Testing of Polymeric Microblades: A Novel Design of Microneedles for Biomedical Applications
Authors: Ebrahiminejad Vahid , Faraji Rad Zahra
Published: September 2022

Conventional microneedles (MNs) are designed as an array of micrometer‐sized projections that can painlessly penetrate the skin. Fabrication of MN arrays can be costly and time‐consuming; additionally, full penetration of an array of MNs with ten to thousands of projections into the skin may not be achievable. This paper reports a new design of MNs known as microblades (MBs) which consist of a singular microstructure. The single integrated design of the MBs reduces the fabrication cost and time, facilitates more effective penetration, and may pave the way for the scale‐up manufacturing of MN devices. Different designs of MBs are fabricated by two‐photon polymerization technique, followed by polydimethylsiloxane micromolding and soft embossing to create replicas. The mechanical integrity of the designs is determined by a series of compression tests. Skin insertion and drug diffusion studies are conducted using a custom‐made applicator to insert the MBs into the porcine abdominal skin to demonstrate delivery of fluorescein tracer. MBs insertion and penetration capabilities and the diffusion of a model drug into a multi‐layered human skin are demonstrated using finite element analysis and 3D diffusion models. The results demonstrate the functional capabilities of the MBs as an alternative to MN arrays.
Quantum Dot/Polymer Bulk Heterostructure Interlayer for Enhanced Charge Collection in AgBiS2 Quantum Dot Photovoltaics
Authors: Park Youngsang , Kim Hyoin , Shin Daekwon , Kim Taewan , Choi Mahnmin , Kim Jugyoung , Lee Doh C. , Jeong Sohee
Published: September 2022

Remarkable progress over the past decade in photovoltaics using solution‐processed nanomaterials as light absorbers has placed colloidal quantum dot (CQD)‐based devices on the map. As such, AgBiS2 CQDs have garnered significant attention as materials exhibiting a high absorptivity with environmentally benign alternatives to Pb‐chalcogenide or Pb halide perovskite‐CQDs. Yet, AgBiS2 CQD‐based solar cells have gravely underperformed compared to Pb‐containing devices, particularly in the metrics of charge carrier extraction from the AgBiS2 absorber, hence its relative mediocrity. To specifically address the extraction efficiency, a bulk heterostructure (QPB) interlayer at the CQD/polymer interface in AgBiS2 CQD solar cells, resulting in an increase of the power conversion efficiency (PCE), e.g., from 5.10% (an average PCE of 4.94 ± 0.11%) to 6.78% (an average PCE of 6.59 ± 0.11%) is deviced. The improved charge extraction at the hole‐collecting interface is responsible for the superior performance, corroborated by high photocurrent (21.5 mA cm–2) and fill factor (67%). The QPB‐interlayered solar cell also gives rise to outstanding durability of the devices, retaining above 95% of the original PCE  for 5 months in ambient air. Our strategy based on an eco‐friendly CQD/polymer could provide an effective route for next‐generation optoelectronics with enhanced charge collection and durability.
A Multifunctional Self‐Assembled Monolayer for Highly Luminescent Pure‐Blue Quasi‐2D Perovskite Light‐Emitting Diodes
Authors: Shin Yun Seop , Ameen Shahid , Oleiki Elham , Yeop Jiwoo , Lee Youngwan , Javaid Saqib , Park Chan Beom , Song Taehee , Yuk Dohun , Jang Hyungsu , Yoon Yung Jin , Lee Woojin , Lee Geunsik , Kim BongSoo , Kim Jin Young
Published: September 2022

Quasi‐2D perovskite materials have promise to unlock the full potential of blue perovskite light‐emitting diodes (PeLEDs). However, the efficiency of blue emissive PeLEDs still lags behind the green‐ and red‐emitting counterparts. Here, a multifunctional passivating molecule of (2‐(3,6‐dichloro‐9H‐carbazol‐9‐yl)ethyl)phosphonic acid (36ClCzEPA) that can form a self‐assembled monolayer (SAM) on the indium tin oxide (ITO) electrode is reported. The 36ClCzEPA SAM facilitates hole injection by increasing the work function of ITO through the strong interfacial dipole layer formation at the interface between the perovskite emitter and the ITO electrode. Moreover, it allows a pure‐blue emission and reduces the exciton quenching of luminescence in the perovskite emitter considerably because of its neutral nature, compared to the commonly used acidic PEDOT:PSS. Furthermore, chlorine atoms in the 36ClCzEPA promote well‐ordered crystalline 2D perovskite phases and decrease interfacial trap‐assisted deactivation channels by interfacial passivation. These beneficial characteristics of the 36ClCzEPA SAM yield the excellent luminescence property of PeLEDs with a maximum luminance of 1253 cd m−2 and a peak external quantum efficiency of 4.80% at 473 nm. This work demonstrates that a well‐designed molecule forming an interfacial SAM can be an important component for enhancing the luminescence property of pure‐blue PeLEDs.
Endohedral funktionalisierte heteroleptische Koordinationskäfige für die Bindung von Phosphatestern
Authors: Platzek André , Juber Selina , Yurtseven Cem , Hasegawa Shota , Schneider Laura , Drechsler Christoph , Ebbert Kristina E. , Rudolf Robin , Yan Qian‐Qian , Holstein Julian J. , Schäfer Lars V. , Clever Guido H.
Published: September 2022

Metallosupramolekulare, nanoskopische Wirte, die als selektive Rezeptoren und Katalysatoren dienen können, bestehen in der Regel je aus nur einem Typ organischer Liganden, was die Vielfalt in Bezug auf die Form der Hohlräume und die Dekoration mit funktionellen Gruppen einschränkt. Wir berichten über eine Reihe von heteroleptischen [Pd2A2B2]‐Koordinationskäfigen, die sich aus einer Bibliothek formkomplementärer bis‐monodentater Liganden auf nicht‐statistische Weise bilden. Ligand A besitzt eine nach innen gerichtete NH‐Funktionalität, die Wasserstoffbrückenbindungen eingehen und mit Amid‐ und Alkylsubstituenten funktionalisiert werden kann. Die Liganden B bestehen aus trizyklischen aromatischen Grundgerüsten unterschiedlicher Form und elektronischer Beschaffenheit. Die so erhaltenen heteroleptischen Koordinationskäfige wurden auf ihre Fähigkeit untersucht, Phosphatdiester als Gäste zu binden. Es wurden atomistische “Molecular Dynamics” (MD) Simulationen in einem expliziten Lösungsmittel durchgeführt, um den Gastbindungsmechanismus im Einklang mit den experimentell ermittelten Affinitäten zu verstehen.
Modulating Supramolecular Charge‐Transfer Interactions in the Solid State using Compressible Macrocyclic Hosts
Authors: Wu Jia‐Rui , Li Dongxia , Wu Gengxin , Li Meng‐Hao , Yang Ying‐Wei
Published: September 2022

Modulating intermolecular charge‐transfer (ICT) interactions between specific donor and acceptor species in host–guest systems is a big challenge and full of research value in supramolecular chemistry and materials science. In this work, a strategy to modulate the supramolecular ICT interactions in the solid state is developed by compressing the binding cavity of a macrocyclic host named perethylated leaning pillar[6]arene (p‐EtLP6). The solid‐state ICT affinities ofp‐EtLP6toward multi‐types of electron‐deficient planar guests could be significantly enhanced by transforming the macrocyclic backbone from the originalpara‐bridged mode into a hybridpara‐ andmeta‐bridged isomeric form (m‐EtLP6). X‐ray single‐crystal structural analyses incorporating theoretical calculation demonstrate that the improved ICT affinities are mainly attributed to the superior host–guest size fit arising from the compressed binding cavity inm‐EtLP6as compared withp‐EtLP6.
Algorithmic Explorations of Unimolecular and Bimolecular Reaction Spaces**
Authors: Zhao Qiyuan , Savoie Brett M.
Published: September 2022

Algorithmic reaction exploration based on transition state searches has already made inroads into many niche applications, but its potential as a general‐purpose tool is still largely unrealized. Computational cost and the absence of benchmark problems involving larger molecules remain obstacles to further progress. Here an ultra‐low cost exploration algorithm is implemented and used to explore the reactivity of unimolecular and bimolecular reactants, comprising a total of 581 reactions involving 51 distinct reactants. The algorithm discovers all established reaction pathways, where such comparisons are possible, while also revealing a much richer reactivity landscape, including lower barrier reaction pathways and a strong dependence of reaction conformation in the apparent barriers of the reported reactions. The diversity of these benchmarks illustrate that reaction exploration algorithms are approaching general‐purpose capability.
Biomolecule‐Based Circularly Polarized Luminescent Materials: Construction, Progress, and Applications
Authors: Dai Yankai , Chen Jingqi , Zhao Chuanqi , Feng Lingyan , Qu Xiaogang
Published: September 2022

Chiral materials related to circularly polarized luminescence (CPL) make up a rapidly developing new field that has broad application prospects in optoelectronic devices, selective recognition, biomedicine, and other fields. Biofunctional chiral materials are also attracting increasing attention because of their unique biocompatibility, chiral recognition, and coding. However, there has been little discussion on biomolecule‐based CPL till now. In this Review, the latest progress in CPL materials related with biomolecules are reviewed, including the chiral construction from molecular level to giant microstructure, as well as their emerging applications. In addition, we discuss the challenges and prospects of bio‐based CPL materials, hoping this work will provide new perspectives and insights for more related research.
The biocomposites properties of compounded poly(lactic acid) with untreated and treated spent coffee grounds
Authors: Xiao Zhi‐Hua , Hou Xu‐Qin , Hwang Shyh‐Shin , Li Hai‐Mei
Published: September 2022

Poly (lactic acid) (PLA) is a biodegradable and environmentally friendly material. And the spent coffee grounds (SCG) are huge waste all over the world. Therefore, the issue that how to convert the low‐value wastes SCG into more valuable products is attracting more research attention. In this work, we compounded PLA with SCG. Firstly, the efficiency of oil extraction from SCG was compared by different methods and solvents. Then, the biocomposites specimens of different SCG contents (0, 5, 10, and 15 wt%) were prepared by extrusion and injection molding. The effects of SCG particle size and content on the thermal and mechanical properties were investigated. Next, the effect of coupling agent (4,4‐methylene diphenyl diisocyanate [MDI]) on the biocomposites properties at 10 wt% SCG was examined by Field emission‐scanning electron microscope and Fourier transform infrared spectroscopy. The results show that the tensile strength and elongation at break of the PLA composites with the optimal contents are increased by about 50% and 120%, respectively, compared with untreated SCG.
Multi‐Ionic Hydrogel with Outstanding Heat‐to‐Electrical Performance for Low‐Grade Heat Harvesting
Authors: Zhou Yongli , Dong Zixian , He Yongjie , Zhu Wentao , Yuan Youlan , Zeng Haoran , Li Chen , Chen Shanshan , Sun Kuan
Published: September 2022

Ionic thermoelectric (i‐TE) materials have attracted much attention due to their ability to generate ionic Seebeck coefficient of tens of millivolts per Kelvin. In this work, we demonstrate that the ionic thermopower can be enhanced by the introduction of multiple ions. The multi‐ionic hydrogel possesses a record thermal‐to‐electrical energy conversion factor (TtoE factor) of 89.6 mV K−1 and an ionic conductivity of 6.8 mS cm−1, which are both better than single salt control hydrogel. Subsequently we build a model to explain thermal diffusion of the ions in multi‐ionic hydrogels. Finally, the possibility of large‐scale integrated applications of multi‐ionic hydrogels is demonstrated. By connecting 7 i‐TEs hydrogels, we obtained an open‐circuit voltage of 1.86 V at ΔT=3 K. Our work provides a new pathway for the design of i‐TEs and low‐grade heat harvesting.
Development of a “turn off–on” whole‐cell biosensor for sulforaphane detection based on the ultrasensitive activator HrpRS
Authors: Li Renjie , Chen Shengyan , Li Yangguang , Chen Xuan , Ye Bang‐Ce
Published: September 2022

Sulforaphane (SFN), a defense secondary metabolite, can be used to predict the health status of plants and also has pharmacological effects, including anticancer, antioxidant, and anti‐inflammatory properties. The detection of SFN is therefore of great significance for the prevention and treatment of diseases. In this study, a “turn off” whole‐cell biosensor that can rapidly and robustly respond to the presence of SFN was constructed based on the orthogonal genetic components (hrpR, hrpS, and PhrpL) of Pseudomonas syringae (PS). The final optimized biosensor, p114(30R‐30S), was able to inhibit 91.7% of the fluorescence intensity in the presence of 100‐μM SFN. Subsequently, a HrpRS‐regulated OFF–ON genetic switch was designed by reconstituting a reverse σ70 promoter on the σ54‐PhrpL promoter sequence; this was coupled with dual‐color reporter genes to construct a “turn off–on” whole‐cell SFN biosensor. The PhrpLB variant increased the expression of green fluorescence a factor of 11.9 and reduced the expression of red fluorescence by 85.8% compared with the system in the absence of SFN. Thus, a robust switching of signal output from “turn off” to “turn on” was realized. In addition, the biosensor showed good linearity in the SFN concentration ranges of 0.1–10 μM (R2 = 0.99429) and 10–100 μM (R2 = 0.99465) and a detection limit of ~0.1 μM.
Handgrip weakness, systemic inflammation indicators, and overall survival in lung cancer patients with well performance status: A large multicenter observational study
Authors: Song Mengmeng , Zhang Qi , Song Chunhua , Liu Tong , Zhang Xi , Ruan Guotian , Tang Meng , Zhang Xiaowei , Xie Hailun , Zhang Heyang , Ge Yizhong , Li Xiangrui , Zhang Kangping , Yang Ming , Li Qinqin , Liu Xiaoyue , Lin Shiqi , Xu Yu , Li Bo , Li Xiaogang , Wang Kunhua , Xu Hongxia , Li Wei , Shi Hanping
Published: September 2022

Background

Systemic inflammation and handgrip weakness have been used to predict mortality in many cancers. The purpose of current study was to evaluate the association of co‐occurrence of inflammation indicators and handgrip weakness with overall survival (OS) of lung cancer (LC) patients with good performance status.

Methods

The cutoff points for handgrip strength (HGS) and the four inflammation indicators were calculated using Maxstat. The time‐dependent receiver operating characteristic curve and C‐index were used to select optimal inflammation indicator for predicting OS of LC patients. The Cox proportional hazard regression model was used to calculate the hazard ratio (HR) of mortality. Kaplan–Meier curves were constructed to evaluate the association of indicators and the OS of LC patients.

Results

Among the 1951 patients, the mean ± standard deviation (SD) age was 60.6 ± 9.9 years, and 1300 (66.6%) patients were male. In patients with good performance status (PS), handgrip weakness (HR, 1.49; 95% confidence interval [95% CI], 1.30–1.70, p < 0.001) and low advanced lung cancer inflammation index (ALI) (HR, 2.05; 95%CI, 1.79–2.34, p < 0.001), high systemic immune‐inflammation index (SII) (HR, 1.91; 95%CI, 1.66–2.19, p < 0.001), high platelet: lymphocyte ratio (PLR) (HR, 1.60; 95%CI, 1.40–1.82, p < 0.001), or high neutrophil: lymphocyte ratio (NLR) (HR, 2.01; 95%CI, 1.76–2.30, p < 0.001) were associated with increased mortality risk of LC patients. ALI had better C‐index (0.624) and time‐AUC in the prediction of OS in LC patients with good PS than other three combinations. The co‐occurrence of handgrip weakness and low ALI more than doubled the risk of death in LC with good PS (HR, 2.44; 95% CI, 2.06–2.89, p < 0.001).

Conclusion

In LC patients who have good PS, patients with combined handgrip weakness and low ALI have the worst prognosis.

The Trial Registration Number

ChiCTR1800020329.
Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy
Authors: Han Mengxue , Li Jinze , Wu Si , Wu Chun , Yu Yongqiang , Liu Yueping
Published: September 2022

Neoadjuvant therapy (NAT) treats early‐stage breast cancers, especially triple‐negative breast cancers (TNBCs). NAT improves pathological complete response (pCR) rates for different breast cancer patients. Recently, immune checkpoint inhibitors that target programmed death 1 (PD‐1) or programmed death ligand 1 (PD‐L1) in combination with NAT have shown antitumor activity in patients with early breast cancer. However, the tumor immune microenvironment (TME) in different subtypes of breast cancers, like TNBC, hormone receptor‐positive (HR+), and human epidermal growth factor receptor 2 amplified (HER2+) and its changes by NAT remain to be fully characterized. We analyzed pre‐NAT tumor biopsies from TNBC (n = 27), HR+ (n = 24), and HER2+ (n = 30) breast cancer patients who received NAT, followed by surgery. The different immune makers (PD‐1, PD‐L1, CD3, and CD8) of tumor‐infiltrating lymphocytes (TILs) were identified with immunofluorescence‐based microenvironment analysis. TILs within cancer parenchyma (iTILs) and in cancer stroma (sTILs) were counted separately. We found that PD‐L1+ cells in tumor and stroma were significantly higher in TNBC patients than in others. PD‐L1+ sTILs were significantly higher in pCR than in non‐pCR patients of all the subtypes. The infiltration scores of B‐cell memory, T‐cell CD4+ memory activated, T‐cell follicular helper, and Macrophage M0 and M1 were relatively higher in TNBC patients, indicating immunoreactive TME in TNBC. Analysis of TCGA‐BRCA RNA‐seq indicated that PD‐L1 was highly expressed in TNBC patients compared with HR+ and HER2+ patients. Higher PD‐L1 expression in TNBC patients was associated with significantly longer overall survival (OS). Our results demonstrated that PD‐L1 expression level of iTILs and sTILs is highest in TNBC among breast cancers. TNBC patients had significantly different immunoreactive TME compared with HR+ and HER2+ patients, suggesting potentially favorable outcomes for immunotherapy in these patients. Also, PD‐L1+ could be a powerful predictor of pCR in TNBC patients after NAT.
A chimeric feeder comprising transforming growth factor beta 1‐ and basic fibroblast growth factor‐primed bone marrow‐derived mesenchymal stromal cells suppresses the expansion of hematopoietic stem and progenitor cells
Authors: Kale Vaijayanti P.
Published: September 2022

Bone marrow‐derived mesenchymal stromal cells (BMSCs) physically associate with the hematopoietic stem cells (HSCs), forming a unique HSC niche. Owing to this proximity, the signaling mechanisms prevailing in the BMSCs affect the fate of the HSCs. In addition to cell−cell and cell‐extracellular matrix interactions, various cytokines and growth factors present in the BM milieu evoke signaling mechanisms in the BMSCs. Previously, I have shown that priming of human BMSCs with transforming growth factor β1 (TGFβ1), a cytokine consistently found at active sites of hematopoiesis, boosts their hematopoiesis‐supportive ability. Basic fibroblast growth factor (bFGF), another cytokine present in the marrow microenvironment, positively regulates hematopoiesis. Hence, I examined whether priming human BMSCs with bFGF improves their hematopoiesis‐supportive ability. I found that bFGF‐primed BMSCs stimulate hematopoiesis, as seen by a significant increase in colony formation from the bone marrow cells briefly interacted with them and the extensive proliferation of CD34+ HSCs cocultured with them. However, contrary to my expectation, I found that chimeric feeders comprising a mixture of TGF‐primed and bFGF‐primed BMSCs exerted a suppressive effect. These data demonstrate that though the TGF‐ and bFGF‐primed BMSCs exert a salutary effect on hematopoiesis when used independently, they exert a suppressive effect when presented as a chimera. These findings suggest that the combinatorial effect of various priming agents and cytokines on the functionality of BMSCs toward the target tissues needs to be critically evaluated before they are clinically applied.
Kinetically Controlled Mn Doping Effect on Composition Tuned CoMn Hydroxide Nanoflakes for Overall Water Splitting Application
Authors: Reddy Jeygeerthika , Duraivel Malarkodi , Senthil Karuppanan , Prabakar Kandasamy
Published: September 2022

The research on cobalt‐based bimetallic hydroxides has led to their emergence as an effective electrocatalyst for oxygen (OER) and hydrogen evolution processes (HER) to split water and replace state‐of‐the‐art efficient noble metals. It is imperative to conduct both the OER and HER in the same electrolyte, hence it is necessary to adjust the material‘s characteristics to be compatible for this application. Due to the Co3+ active site, Co(OH)2 is electrochemically oxidized to CoOOH and exhibits outstanding OER kinetics. The incorporation of Mn into the cobalt hydroxide matrix increases the surface area while balancing the ratio of *OH to *O radicals to increase electrocatalytic activity. The complementary effects of the two metal hydroxides (Co and Mn) reveal a fresh perspective on the next‐generation electrocatalyst. The OER and HER reactions are both optimized using an easy electrodeposition method. The best HER and OER as two‐electrode electrolyzers displayed a cell voltage of 1.69 V at 10 mA/cm2 in alkaline electrolyte. Interestingly, when the state of art material Pt deposited on nickel foam substrate used for HER and the best CoMn hydroxide used for OER exhibits a cell voltage of only 1.55 V to drive the current density of 10 mA/cm2.
Progress and challenges of prelithiation technology for lithium‐ion battery
Authors: Huang Zhenyu , Deng Zhe , Zhong Yun , Xu Mingkang , Li Sida , Liu Xueting , Zhou Yu , Huang Kai , Shen Yue , Huang Yunhui
Published: September 2022

Prelithiation technology is widely considered a feasible route to raise the energy density and elongate the cycle life of lithium‐ion batteries. The principle of prelithiation is to introduce extra active Li ions in the battery so that the lithium loss during the first charge and long‐term cycling can be compensated. Such an effect does not need to change the major electrode material or battery structure and is compatible with the majority of current lithium‐ion battery production lines. At this stage, various prelithiation methods have been reported, some of which are already in the pilot‐scale production stage. But there is still no definitive development roadmap for prelithiation. In this review, we first introduce the influence of prelithiation on electrochemical performance from a theoretical point of view and then compare the pros and cons of different prelithiation methods in different battery manufacturing stages. Finally, we discuss the challenges and future development trends of prelithiation. We aim to build up a bridge between academic research and industrial application. Some engineering problems in the promotion of prelithiation technique are extensively discussed, including not only the implementation of prelithiation but also some collateral issues on battery designing and management.
Top advances of the year: Pediatric oncology
Authors: Pappo Alberto S. , Karol Seth E. , Bertrand Kelsey C.
Published: September 2022

Accelerated discovery and collaborative research continue to highlight the remarkable progress that has been made in the diagnosis and treatment of pediatric cancers. This manuscript highlights important discoveries on how precision oncology is being incorporated into the diagnosis and treatment of childhood cancer at the national level to identify promising new therapies using a tumor‐agnostic approach. In addition, we have highlighted three articles that incorporate genomics and cell‐free DNA to better classify, monitor and incorporate risk‐based therapies for children with medulloblastoma. Finally, we highlighted the important role of monclonal antiobody therapy in the treatment of recurrent B‐cell leukemia and newly diagnosed high‐risk neuroblastoma.
Electrochemical Performance of High‐Valence Mo6+ and Low‐Valence Mn2+ Doped‐ Na3V2(PO4)3@C Cathode for Sodium‐Ion Batteries
Authors: Meghnani Dipika , Kumar Singh Shishir , Srivastava Nitin , Kumar Tiwari Rupesh , Mishra Raghvendra , Patel Anupam , Tiwari Anurag , Kumar Singh Rajendra
Published: September 2022

The sodium superionic conductor (NASICON)‐Na3V2(PO4)3 (NVP) is an attractive cathode for sodium‐ion batteries, which is still confronted with limited rate performance due to its low electronic conductivity. In this paper, a chemical strategy is adopted to partially replace V3+ of the NVP framework by low‐valence Mn2+ and high‐valence Mo6+ substitution. The crystal structure, sodium‐ion diffusion coefficient and electrochemical performance of Mn−Mo‐doped [Na3.94V0.98Mo0.02Mn(PO4)3@C] cathode were investigated. X‐ray diffraction confirmed the NASICON‐type structure and XPS analysis confirmed the oxidation state of Mn and Mo in doped NVP cathode. The Na ion diffusion processes were inferred from Cyclic Voltammetry (CV), Galvanostatic intermittent titration technique (GITT) and Electrochemical Impedance Spectroscopy (EIS) measurement, which clearly show rapid Na‐ion diffusion in NASICON‐type cathode materials. The Mn−Mo‐substituted NVP shows smoother charge‐discharge profiles, improved rate performance (64.80 mAh/g at 1 C rate), better energy density (308.61 mWh/g) and superior Na‐ion kinetics than that of unsubstituted NVP@C cathode. Their enhanced performance is attributed to large interstitial volume mainly created by high valence Mo6+ and enhanced capacity is attributed to the low valence Mn2+ doping. These results demonstrate that Mn−Mo‐doped NVP cathode is strongly promising cathode material for sodium‐ion batteries.
A Reconfigurable Nanophotonic Heterostructure Engineered by a DNA Origami Switch
Authors: Ge Huan , Yang Donglei , Li Yimeng , Wei Yongji , Zhu Xinyuan , Wang Pengfei , Zhang Chuan
Published: September 2022

DNA origami has been widely used to construct nanophotonic structures due to its unparallel capability in assembling photonic nanomaterials with nanometer precision. Nevertheless, the majority of fabricated fluorescence‐based nanophotonic systems so far operate in the ultraviolet‐visible (UV‐Vis) region, which are accompanied by limitations of shallow penetration and potential light damage. Herein, we constructed a reconfigurable nanophotonic heterostructure by integrating an upconversion nanoparticle (UCNP) and a gold nanorod (AuNR) on a DNA origami switch (DOS) template. With the unique anti‐Stokes luminescence of UCNP whose excitation wavelength is mostly located in the near‐infrared (NIR) region, the obtained reconfigurable nanophotonic system can be excited by 980 laser light and generates visible light emission. In our nanophotonic system, the DNA origami template serves as a switch to reversibly tune the optical properties of UCNP. The construction of this nanophotonic heterostructure expands the toolbox of DNA origami‐based nanophotonic systems that may hold great potential in optical biosensing and imaging.
α‐Pinene inhibits the growth of cervical cancer cells through its proapoptotic activity by regulating the miR‐34a‐5p/Bcl‐2 signaling axis
Authors: Huang Xiaosu , Yan Pei , Ding Wenqing , Zhou Chang , Xu Qiuxiang , Li Ming , Ye Lianbao , Chen Weiqiang
Published: September 2022

Among gynecological tumors, cervical cancer (CC) has the second‐highest prevalence and mortality rate. α‐Pinene is a bicyclic monoterpenoid compound extracted from pine needles that carried promising anticancer properties. Nevertheless, its effect on CC and the underlying mechanism has not yet been elucidated. Therefore, we investigated the effect of α‐Pinene on apoptosis in CC via in vitro assays of flow cytometry (FCW), terminal deoxynucleotidyl transferase‐mediated nick end labeling (TUNEL) assay, quantitative real‐time polymerase chain reaction (qRT‐PCR), and Western blot. Following that, we detected the proapoptotic function of α‐Pinene on HeLa cells in vivo by TUNEL assay and immunofluorescence staining. Our results displayed that the α‐Pinene inhibited the growth of HeLa cells and stalled the cells in the G0/G1 phase. Interestingly, we also detected that α‐Pinene induced HeLa cells to apoptosis. The results investigated that α‐Pinene induced HeLa cells apoptosis along with up‐regulating the expression of Bax, Bid, caspase‐9, caspase‐3, miR‐34a‐5p, and down‐regulating the expression of Bcl‐2 in vitro. At the same time, the expression levels of target genes in vivo were consistent with those in vitro. Our experiment proved that α‐Pinene promoted apoptosis, which will be used to hopefully maximize the therapeutic strategies in clinical studies in CC.
Evapotranspiration in a subtropical wetland savanna using low‐cost lysimeter, eddy covariance and modelling approaches
Authors: Saha Amartya , Boughton Elizabeth H. , Li Haoyu , Sonniér Gregory , Gomez‐Casanovas Nuria , McMillan Nicholas , Zhang Xukai
Published: September 2022

Evapotranspiration (ET) constitutes the largest loss of water from subtropical grassland and wetland ecosystems, yet data in much of the world have high uncertainty at the landscape scale as there is little information on plant water use. Additionally, anthropogenic alterations to grasslands are a major threat globally and alter ecosystem water use, but the impact of these changes is often unquantified. A major reason for this is the complexity and expense of field‐based ET quantification methods such as agricultural lysimeters and eddy covariance systems. Accurate measurements of ET are critical for sustainable water management. This study developed two different low‐cost lysimeters—weighing‐type and water level‐based, to measure ET under partly controlled conditions for single species as well as mixed grassland and wetland communities. Lysimeters were placed in an open‐sided, transparent‐roofed shadehouse and watered periodically. ET values were then compared with (i) actual ET from an eddy covariance tower onsite, (ii) vapour transport‐based reference ET models (FAO Penman–Monteith, modified Turc and Abtew simple radiation models), and (iii) reference ET data customized for vegetation types from the Florida Automated Weather Network (FAWN). Both weighing‐type and water level lysimeters yielded seasonal patterns and annual magnitudes similar to other ET methods. Annual ET measurements from single‐species weighing‐type lysimeters (ranging from 881 to 1278 mm for four plant species, n = 5 per species, 20 in total) and water level lysimeters (1085 ± 306 mm, plant community average, n = 31) were about 10–20% lower than reference ET models (~1300 mm) and similar to FAWN data (1050 mm). Actual ET from eddy covariance was 722 mm for 10 months (missing data for February and March), while weighing lysimeter measurements for the dominant grass Paspalum notatum was 885 mm for the same 10 months. While rainfall exclusion and watering can result in ET differing from actual field conditions, low‐cost lysimeters can provide an independent measure of ET for comparison with regional ET models/remote sensing data lacking field validation. Thereby, low‐cost lysimeters are potentially useful for water resources and ecosystem management in data‐poor regions of the world.
IL‐3 regulates the differentiation of pathogenic Th17 cells
Authors: Rani Lekha , Kumar Anil , Karhade Juilee , Pandey Garima , Guha Adrita , Mishra Gyan C. , Wani Mohan R.
Published: September 2022

IL‐17‐producing Th17 cells play an important role in pathogenesis of rheumatoid arthritis (RA). Aberrant immune activation due to an imbalance between Th17 and regulatory T (Treg) cells is associated with the development of RA and other autoimmune diseases. Targeting pathogenic Th17 cells and their associated molecules is emerging as a promising strategy to treat and reverse RA. Here, we demonstrate that IL‐3 inhibits the differentiation of Th17 cells and promotes the development of Treg cells in IL‐2‐dependent manner. In IL‐2 KO mice, we observed that IL‐3 has no effect on differentiation of both Th17 and Treg cells. In addition, IL‐3 decreases pathogenic IL‐17A+TNF‐α+, IL‐17A+IFN‐γ+ and IL‐23R+ Th17 cells, secretion of GM‐CSF and IFN‐γ, and osteoclastogenesis when presented in the culture together with Th17 polarizing cytokines. Mechanistically, IL‐3 regulates the development of Th17 cells through the inhibition of STAT3 phosphorylation. IL‐3 treatment significantly decreases the pathogenic Th17 cell responses and arthritic scores in the mouse model of RA. Importantly, IL‐3 inhibits the differentiation of human Th17 cells. Thus, our results suggest a novel therapeutic role of IL‐3 in the regulation of Th17 cell‐mediated pathophysiology of RA.
Termination of CD40L co‐stimulation promotes human B cell differentiation into antibody‐secreting cells
Authors: Marsman Casper , Verstegen Niels JM , Streutker Marij , Jorritsma Tineke , Boon Louis , ten Brinke Anja , van Ham S. Marieke
Published: September 2022

Human naïve B cells are notoriously difficult to differentiate into antibody‐secreting cells (ASCs) in vitro while maintaining sufficient cell numbers to evaluate the differentiation process. B cells require T follicular helper (TFH) cell‐derived signals like CD40L and IL‐21 during germinal center (GC) responses to undergo differentiation into ASCs. Cognate interactions between B and TFH cells are transient; after TFH contact, B cells cycle between GC light and dark zones where TFH contact is present and absent, respectively. Here, we elucidated that the efficacy of naïve B cells in ACS differentiation is dramatically enhanced by the release of CD40L stimulation. Multiparameter phospho‐flow and transcription factor (TF)‐flow cytometry revealed that termination of CD40L stimulation downmodulates NF‐κB and STAT3 signaling. Furthermore, the termination of CD40 signaling downmodulates C‐MYC, while promoting ASC TFs BLIMP1 and XBP‐1s. Reduced levels of C‐MYC in the differentiating B cells are later associated with crucial downmodulation of the B cell signature TF PAX5 specifically upon the termination of CD40 signaling, resulting in the differentiation of BLIMP1 high expressing cells into ASCs. The data presented here are the first steps to provide further insights how the transient nature of CD40 signaling is in fact needed for efficient human naïve B cell differentiation to ASCs.
Calix[4]arene‐Based Sensitizers for Host‐Guest Supramolecular Dyads for Solar Energy Conversion in Photoelectrochemical Cells.
Authors: Decavoli Cristina , Boldrini Chiara L. , Faroldi Federica , Baldini Laura , Sansone Francesco , Ranaudo Anna , Greco Claudio , Cosentino Ugo , Moro Giorgio , Manfredi Norberto , Abbotto Alessandro
Published: September 2022

The photogeneration of electricity and solar fuels by solar irradiation in photoelectrochemical cells is one of the sectors with the highest growth potential in the decarbonised society. However, the use of different components, in particular photosensitizers and catalysts, can present problems of charge transfer efficiency at the interface, leading to lower final efficiencies. In this work we present novel integrated photosensitizer‐catalyst dyads based on robust and, at the same time, flexible host‐guest non‐covalent interactions through the use of calix[4]arene cavities. Current photogeneration in photoelectrochemical cells showed twice greater efficiency in the integrated calixarene‐based host‐guest dyads compared to the traditional architecture based on the separate photosensitizer‐catalyst pair. Molecular dynamics studies have shown that the enhanced performance originates from an optimization of the distances between the centres of the photosensitizer, catalyst and semiconductor involved in the charge transfer processes, thus allowing a higher final efficiency of the charge photogeneration process.