bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Virtue Reliabilism Explain the Value of Knowledge?
Authors: Brogaard Berit
Published: January 2007

I Introduction

A fundamental intuition about knowledge is that it is more valuable than mere true belief. This intuition is pervasive. We have an almost universal desire to know and nearly no desire to believe the truth accidentally. However, it turns out to be extremely difficult to explain why knowledge is more valuable. Linda Zagzebski and others have called this the ‘value problem.’ They argue that the value problem is particularly difficult to unravel for generic reliabilism. According to generic reliabilism, knowledge is true belief produced by reliable belief-forming processes or faculties. But, the critics argue, ‘the reliability of the source of a belief cannot explain the [value difference] between knowledge and true belief.’ For reliably formed beliefs allegedly are valuable only insofar as they tend to be true.
Baudelaire et la sculpture ennuyeuse de son temps
Authors: Hamrick Lois Cassandra Streett
Published: January 2007

To understand the significance of Baudelaire's apparent diatribe against sculpture in his Salon of 1846, Hamrick reconstructs the contemporary discourse within which Baudelaire and other forwarding-looking critics were reassessing the place of sculpture in creative expression. She brings to light allusions and similarities in critical commentary to reveal the presence of a submerged ideolect, elements of which can already be found in the 1830s in Gautier's critique of contemporary neoclassical sculpture, in Vivant Denon's note to an engraving of "primitive" art objects, some of which were exhibited at the Musée de la Marine, and in the window displays of sculpted "marchandises fétiches." Hamrick concludes that Baudelaire's attack is not aimed at sculpture per se, nor at the art de Caraïbes, but at the monotonous replication of neoclassical models and the trivialization of sculpture through the serialization of miniature figures for a commerce-minded bourgeois public. (In French)
Nonredundant Role of Akt2 for Neuroprotection of Rod Photoreceptor Cells from Light-Induced Cell Death
Authors: Li Guiyuan , Anderson Robert E. , Tomita Hiroshi , Adler Ruben , Liu Xiaochun , Zack Donald J. , Rajala Raju V. S.
Published: January 2007

The Akt kinases mediate cell survival through phosphorylation and inactivation of apoptotic machinery components. Akt signaling provides a trophic signal for transformed retinal neurons in culture, but thein vivorole of Akt activity is unknown. In this study, we found that all three Akt isoforms were expressed in rod photoreceptor cells. We investigated the functional roles of Akt1 and Akt2, two of the isoforms of Akt, and their biological significance in light-induced retinal degeneration. Consistent with the hypothesis that Akt activity is important to circumvent stress-induced apoptosis, herein we report the novel finding that rod photoreceptor cells in Akt2 knock-out mice exhibited a significantly greater sensitivity to stress-induced cell death than rods in heterozygous or wild-type mice. Under similar conditions, Akt1 deletion had no effect on the retina. The presence of three Akt isoforms in the retina is suggestive of a functional redundancy; however, our studies clearly demonstrate that, under stress, Akt1 and Akt3 cannot complement the specific survival signals driven by Akt2. Furthermore, we show that Akt2 is specially activated is response to light stress. The results presented in this study provide the first direct evidence that Akt2 has a nonredundant neuroprotective role in photoreceptor survival and maintenance.
Taste-Evoked Responses to Sweeteners in the Nucleus of the Solitary Tract Differ between C57BL/6ByJ and 129P3/J Mice
Authors: McCaughey Stuart A.
Published: January 2007

C57BL/6ByJ (B6) and 129P3/J (129) mice have different alleles ofTas1r3, which is thought to influence gustatory transduction of sweeteners, but studies have provided conflicting results regarding differences in sweetness perception between these strains. Single-unit taste-evoked activity was measured in the nucleus of the solitary tract (NST) in anesthetized B6 and 129 mice to address this controversy and to provide the first electrophysiological characterization of this nucleus in mice. Neurons had properties similar to those of NST cells in other species, including mean breadth-of-tuning of 0.8 ± 0.0. There were no strain differences in neural responses at 600 or 900 ms after onset, but, with a 5 s evoked period, responses to the sweeteners sucrose, maltose, acesulfame-K, SC-45647, andd-phenylalanine were significantly larger in B6 relative to 129 mice. The strains did not differ in their mean response to NaSaccharin, but it evoked an across-neuron pattern of activity that was more similar to that of sucrose and less similar to that of NaCl in B6 mice compared with 129 mice. Neurons were classified as sucrose, NaCl, or HCl responsive, with the former more common in B6 than 129 mice. Relative to other neurons, sucrose-responsive cells had delayed but more sustained sweetener responses in both strains. The results suggest that B6 mice perceive some sweeteners as more intense, but NaSaccharin as sweeter and less salty, relative to 129 mice. Furthermore, activity evoked by sweeteners includes a phasic response sent to different NST cells than a later tonic response, and only the latter differs between B6 and 129 mice.
Potentiation of Exocytosis by Phospholipase C-Coupled G-Protein-Coupled Receptors Requires the Priming Protein Munc13-1
Authors: Bauer Claudia S. , Woolley Robert J. , Teschemacher Anja G. , Seward Elizabeth P.
Published: January 2007

The vesicle priming protein Munc13-1 is regulated by diacylglycerol (DAG) and is therefore hypothesized to play a role in the control of neurotransmitter release by phospholipase C (PLC)-coupled receptors. We combined voltage-clamp recordings of voltage-gated Ca2+channels (VGCCs) and high-resolution capacitance measurements to investigate the mechanism of receptor-mediated modulation of exocytosis in bovine chromaffin cells. Activation of endogenous H1Gq-protein-coupled receptors (GqPCRs) by histamine potentiated stimulus-coupled secretion despite concurrently inhibiting Ca2+influx through VGCCs. Histamine increased the size of the readily releasable pool of vesicles and in particular a subpool of fusion-competent vesicles localized in close proximity to VGCCs. Pharmacological characterization showed that potentiation of exocytosis depended on the activation of PLC but not protein kinase C. Overexpression of wild-type Munc13-1 by adenoviral infection had no effect on histamine-induced potentiation per se, whereas DAG-insensitive Munc13-1H567Kcompletely abolished it.

This is the first endogenous mammalian GqPCR signaling pathway identified that engages Munc13-1 to increase stimulus-coupled secretion by recruiting vesicles to the immediately releasable pool. GqPCRs are therefore able to control exocytosis at the level of SNARE (solubleN-ethylmaleimide-sensitive factor attachment protein receptor) complex formation to produce rapid, short-term potentiation of the secretory output of neurons and endocrine cells.
Biplot analysis of genotype-environment interaction in durum wheat using the AMMI model
Authors: Farshadfar E. , Sutka J.
Published: January 2007

The genotype by
environment (GE) interaction is a major problem in the study of quantitative
traits because it complicates the interpretation of genetic experiments and
makes predictions difficult. In order to quantify GE interaction effects on the
grain yield of durum wheat and to determine stable genotypes, field experiments
were conducted with ten genotypes for four consecutive years in two different
conditions (irrigated and rainfed) in a completely randomized block design with
three replications in each environment. Combined analysis of variance exhibited
significant differences for the GE interaction, indicating the possibility of
stable entries. The results of additive main effect and multiplicative
interaction (AMMI) analysis revealed that 12% of total variability was
justified by the GE interaction, which was six times more than that of
genotype. Ordination techniques displayed high differences for the interaction
principal components (IPC1, IPC2 and IPC3), indicating that 92.5% of the GE sum
of squares was justified by AMMI1, AMMI2 and AMMI3, i.e. 4.5 times more than
that explained by the linear regression model. The results of the AMMI model
and biplot analysis showed two stable genotypes with high grain yield, due to
general adaptability to both rainfed and irrigated conditions, and one with
specific adaptation.
Treatment of Feline Mammary Fibroepithelial Hyperplasia Following a Single Injection of Proligestone
Authors: Vitásek R. , Dendisová H.
Published: January 2007

A case of fibroepithelial hyperplasia of the mammary gland in the cat is reported. A seven-monthold female cat was presented for diffuse enlargement of all of the mammary glands. The cat was treated with proligestone (Covinan®) for the suppression of estrus. Four weeks later all 8 mammary glands were asymmetrically enlarged. There was ulceration of one gland. Sonographic imaging of the affected mammary glands showed homogeneous and granular structures. The patient was treated with subcutaneous injections of 10 mg/kg aglépristone (Alizine®) on days 1, 2, 7, 14 and 21. Within six weeks the mammary glands had completely regressed. No side effects were observed. It is the first case of fully documented feline mammary fibroepithelial hyperplasia and its treatment in the Czech Republic.
Telehealth Treatment for Opioid Use Disorder During Pregnancy
Authors: Coffey M. Justin , Weng Maxwell , Jimes Cynthia , Brigham Shannon , Lira Marlene C.
Published: March 2024

This cohort study evaluates opioid use disorder (OUD) treatment and pregnancy outcomes among pregnant patients receiving OUD care through a multistate telemedicine program in the US.
Association of Conjunctival Ulceration With Pembrolizumab
Authors: Kuhar Benjamin , Bailey James , Aeum Judy
Published: March 2024

This case report describes a patient with conjunctival ulceration following pembrolizumab therapy for breast cancer.
Energy Absorption Capability of Graded Hybrid Triply Periodic Minimal Surface Structures Based on Fracture Zone Controlling
Authors: Shi Xin , Jiang Weimin , Song Kanghui , Zhang Changdong , Liu Tingting , Liao Wenhe
Published: March 2024

A novel design strategy of the graded hybrid energy‐absorbing lattice structure is proposed by controlling fracture zone. The primitive (P) and iWP (W) structures are two kinds of triply periodic minimal surface structures with typical deformation and failure modes. Thus, taking the P (stretching‐dominated) and the W structures (bending‐dominated) as object, the deformation and failure mechanisms of two structures are studied. Then, the PWP (i.e., the fracture zone of the P structure filling with the W structure) and WPW (i.e., the fracture zone of the P structure filling with the W structure) structures with uniform and gradient change are designed. The structures are fabricated using stereolithography appearance process and compressed under quasistatic conditions. And the energy absorption capacity comparison of these structures is studied. The experimental results show that the maximum energy absorption efficiency of the PWP structure is 38.85% higher than that of the P structure and the densification energy absorption of the WPW structure is 66.67% higher than that of the W structure. Additionally, gradient design can effectively improve the densification energy absorption of lattice structure. The novel structural design greatly contributes to customized energy absorption design of lattice structures.
Bioprinting Macroporous Hydrogel with Aqueous Two‐Phase Emulsion‐Based Bioink: In Vitro Mineralization and Differentiation Empowered by Phosphorylated Cellulose Nanofibrils
Authors: Wang Qingbo , Karadas Özge , Rosenholm Jessica M. , Xu Chunlin , Näreoja Tuomas , Wang Xiaoju
Published: March 2024

Aqueous two‐phase emulsion (ATPE)‐based bioinks, a creative innovation for bioprinting, enable the fabrication of complex 3D cell‐laden hydrogels with macroporous structure, which promote cellular activities within the scaffold. However, these bioinks intrinsically lack stability and specific biofunctionality, potentially limiting their application for targeted tissue engineering. This study proposes a new perspective by introducing less than 0.1% phosphorylated cellulose nanofibrils (pCNF), a 1D nanofibril top‐down produced from natural biomasses, into a dextran/methacrylated gelatin (GelMA)‐based ATPE system for extrusion‐based bioprinting of preosteoblastic cells, aiming to fabricate macroporous hydrogels with osteogenic differentiation potential. The pCNF that is selectively partitioned in the GelMA phase can not only improve the emulsion stability and alter the rheological behaviors of the ATPE‐based bioink, but also enhance the damping capacity and mineralization ability of the crosslinked hydrogels. Furthermore, macroporous hydrogels with pCNF demonstrate increased cell activity and higher viability in post‐printing, along with higher alkaline phosphatase activity and osteoblastic gene expression. Importantly, the organized interfaces within the hydrogel facilitate the formation of macroscopic biomineralized nodules in vitro. The incorporation of multifunctional pCNF in the ATPE system significantly boosts the physiochemical and biological performance of the macropore‐forming bioink, transforming them into a suitable platform for engineering in vitro bone models.
Anion Hybridization for Enhanced Broadband Optical Response in Bi‐Doped Photonic Glass and Fiber
Authors: Yang Wangming , Dong Quan , Huang Yupeng , Lin Quanhua , Zhang Ke , Chen Jingfei , Li Xueliang , Zhou Shifeng
Published: March 2024

Given the ever‐increasing demand for transmission capacity in optical fiber communication systems, there is a growing focus on developing active fibers and devices with an optical response across a wider spectrum. Bismuth (Bi)‐doped photonic glasses have attracted significant interest for their exceptional ultra‐broadband optical response, particularly within telecommunication bands. However, developing advanced Bi‐activated materials with robust optical response, high compatibility with commercial transmission systems, and low processing temperature remains a huge challenge. Herein, an anion hybridization strategy is proposed to overcome the aforementioned limitations. The anion hybridization significantly enhances the broadband optical response (≈10 times) of the Bi center following the introduction of fluorine ions, and reduces the transition temperature of the photonic glass (≈200 °C). Moreover, the near‐infrared optical response bandwidth experiences significant broadening, a result attributed to the larger inhomogeneous broadening. Furthermore, successful fabrication of the anion‐hybridized Bi‐activated glass fiber is achieved, demonstrating excellent compatibility with commercial transmission fibers. Additionally, the fabricated fiber exhibits an amplified spontaneous emission and on‐off gain across a broad waveband, further validating its efficacy. These results indicate that anion hybridization offers an effective strategy to optimize the optical and thermal properties of photonic materials to develop novel advanced photonic devices.
High Quality Near‐Infrared Single‐Mode Lasing from γ‐InSe Using a Transferrable Planar Microcavity
Authors: Ge Anping , Sun Liaoxin , Xie Maobin , Cui Henyi , Zhou Dongjie , Ma Lei , Zhang Xin , Huan Yanlin , Tian Haoyang , Jing Wenji , Yao Bimu , Wang Shaowei , Shen Xuechu , Lu Wei
Published: March 2024

The on‐chip near‐infrared (NIR) lasing devices based on van der Waals (vdW) layered materials are highly desired owing to their widespread applications in optoelectronic communication, computing, and sensing. However, the single‐mode NIR lasing devices with superior performance based on vdW layered materials are hard to obtain because of complex and meticulous microcavity structure and the damage to layered materials during preparation. Here, a high‐quality NIR single‐mode lasing device in γ‐phase indium selenide (γ‐InSe) is achieved by using a transferrable planar microcavity. The single‐mode lasing devices based on distributed Bragg reflectors microcavity and super Tamm structure can be simply prepared with quality factors up to 5710 and 3526, respectively. And angle‐resolved spectra show that the lasing device has high directionality with divergence angle <5°. Moreover, the wavelength of lasing device can be tuned ≈30 nm by varying the cavity length via thickness control of γ‐InSe layer. These results not only suggest that γ‐InSe is a promising material for NIR lasing devices, but also present a simple and effective approach for preparing high‐quality lasing devices utilizing other vdW layered materials.
Enhancing Photocurrent Efficiency in Filter‐Less NIR Organic Photodetectors Through a Photomultiplication‐Inducing Perovskite Quantum Dot Interlayer
Authors: Jeong Minyoung , Han Se Gyo , Park Byeongchan , Choi Jinhyeok , Chung Sein , Lee Dongki , Cho Kilwon
Published: March 2024

A unique charge‐injection‐narrowing organic photodetector (CIN OPD) is demonstrated for near‐infrared (NIR) range operation. In conventional CIN OPDs, photomultiplication (PM) is achieved within a bulk heterojunction (BHJ) active layer with a donor:acceptor ratio of 100:1. Unfortunately, this approach encounters an issue in which the narrowband detection wavelength is determined solely by an excessive donor quantity. Consequently, the conventional devices face a critical limitation in that their detection range cannot extend to longer wavelengths. However, this limitation has been overcome through a novel mechanism and have fabricated a device that responds at λ = 940 nm. When a perovskite quantum dot interlayer is inserted as the PM‐inducing layer, PM occurs outside the active layer. Therefore, the BHJ active layer is structured with a donor:acceptor ratio of 50:50, resulting in an extension of the detection wavelength to the absorption tail of the narrow‐bandgap acceptor. The device demonstrates a remarkable external quantum efficiency (EQE) of 39 000% with a narrow full‐width at half‐maximum (FWHM) of 98 nm at 60 V. It also has a high specific detectivity and a short response time. The device represents a significant advancement in filter‐free, high‐efficiency photodetectors suitable for optical sensor applications such as light detection and ranging (LiDAR).
Achieving Low Cost and High Performance Flexible CsPbIBr2 Perovskite Photodetectors Arrays with Imaging System via Dual Interfacial Optimization and Structural Design
Authors: Zhao Yue , Jiao Shujie , Yang Song , Wang Dongbo , Gao Shiyong , Wang Jinzhong
Published: March 2024

All‐inorganic metal halide perovskites are competitive candidate as next‐generation flexible photodetectors (PDs) materials due to the remarkable photoelectric properties, enhanced heat stability, and mechanical flexibility. However, constructing low‐cost flexible perovskites PDs with high photodetection performance, good operation stability and mechanical robustness, and manufacturing corresponding flexible PDs array have been a challenge. Herein, the PbCl2 and Zinc(II) Dibenzyldithiocarbamate (Zn(DBDTC)2) are employed to modify bottom and top interface of CsPbIBr2 perovskite layer, respectively, to passivate surface trap state, enhance hydrophobicity and resist phase segregation, and improve interface contact. Consequently, the self‐powered champion PDs with low‐cost Bi2Te3 electrode reach a responsivity of 0.38 A W−1 and a maximum detectivity of 3.44 × 1013 Jones at 570 nm, and maintain the outstanding long‐term and operational stability without additional encapsulation. Meanwhile, the HTL‐free flexible PDs based on low‐temperature CsPbIBr2 perovskite layer exhibit impressive photodetection performance and mechanical robustness in bending test. More importantly, the flexible PDs array (5 × 5 pixels) and corresponding imaging system are fabricated with uniform and clear imaging results under flatting and bending state. This research is of great significance for the application of stable and high‐performance inorganic perovskites PDs and flexible array imaging systems.
Self‐Assembled 2D Sheets of an Amphiphilic Sexiphenyl Exhibit Intense Polarized Blue Emission in the Solid State
Authors: Mondal Pramita , Hill Jonathan P. , Manna Gouranga , De Dalui Sharmistha , Neal Edward A. , Richards Gary. J. , Ariga Katsuhiko , Yamauchi Yusuke , Shrestha Lok Kumar , Acharya Somobrata
Published: March 2024

Distinct from inorganic 2D nanomaterials (e.g., graphene, MoS2, etc,), self‐assembled organic 2D materials are significant due to the unique advantages of fine structure tunability and functionality. Electronically and photofunctionally‐active compounds (e.g., pentacene, p‐sexiphenyl) are highly attractive for applications but are limited by difficult handling and the existence of only a few native structures of the compounds. Here, it is shown that a p‐sexiphenyl derivative incorporated into 2D multilamellar sheets with chromophores oriented in the layers exhibits a significant polarization of photoluminescence. Highly emissive, amphiphilic sexiphenyl with hydrophilic/hydrophobic groups self‐assembles at air–water interface with chromophore orientation in the resulting films being controlled by monolayer compression. Large‐area multilamellar structures with p‐sexiphenyl chromophores highly oriented against the 2D plane are prepared by consecutive film transfers. The 2D sheets exhibit significant polarization of photoluminescence with polarization ratio 0.8 between orthogonal in‐plane axes. Notably, multilamellar structures cannot be established for the same p‐sexiphenyl using thermotropic processing thus emphasizing the importance of the 2D sheet multilayer synthesis process. Amphiphile design can be applied for the tailored synthesis of large‐area multilayered 2D sheets and used to construct highly efficient light‐emitting devices.
Neurotoxic Microglial Activation via IFNγ‐Induced Nrf2 Reduction Exacerbating Alzheimer's Disease
Authors: Kang You Jung , Hyeon Seung Jae , McQuade Amanda , Lim Jiwoon , Baek Seung Hyun , Diep Yen N. , Do Khanh V. , Jeon Yeji , Jo Dong‐Gyu , Lee C. Justin , Blurton‐Jones Mathew , Ryu Hoon , Cho Hansang
Published: March 2024

Microglial neuroinflammation appears to be neuroprotective in the early pathological stage, yet neurotoxic, which often precedes neurodegeneration in Alzheimer's disease (AD). However, it remains unclear how the microglial activities transit to the neurotoxic state during AD progression, due to complex neuron‐glia interactions. Here, the mechanism of detrimental microgliosis in AD by employing 3D human AD mini‐brains, brain tissues of AD patients, and 5XFAD mice is explored. In the human and animal AD models, amyloid‐beta (Aβ)‐overexpressing neurons and reactive astrocytes produce interferon‐gamma (IFNγ) and excessive oxidative stress. IFNγ results in the downregulation of mitogen‐activated protein kinase (MAPK) and the upregulation of Kelch‐like ECH‐associated Protein 1 (Keap1) in microglia, which inactivate nuclear factor erythroid‐2‐related factor 2 (Nrf2) and sensitize microglia to the oxidative stress and induces a proinflammatory microglia via nuclear factor kappa B (NFκB)‐axis. The proinflammatory microglia in turn produce neurotoxic nitric oxide and proinflammatory mediators exacerbating synaptic impairment, phosphorylated‐tau accumulation, and discernable neuronal loss. Interestingly, recovering Nrf2 in the microglia prevents the activation of proinflammatory microglia and significantly blocks the tauopathy in AD minibrains. Taken together, it is envisioned that IFNγ‐driven Nrf2 downregulation in microglia as a key target to ameliorate AD pathology.
Integration Analysis of Single‐Cell Multi‐Omics Reveals Prostate Cancer Heterogeneity
Authors: Bian Xiaojie , Wang Wenfeng , Abudurexiti Mierxiati , Zhang Xingming , Ma Weiwei , Shi Guohai , Du Leilei , Xu Midie , Wang Xin , Tan Cong , Sun Hui , He Xiadi , Zhang Chenyue , Zhu Yao , Zhang Min , Ye Dingwei , Wang Jianhua
Published: March 2024

Prostate cancer (PCa) is an extensive heterogeneous disease with a complex cellular ecosystem in the tumor microenvironment (TME). However, the manner in which heterogeneity is shaped by tumors and stromal cells, or vice versa, remains poorly understood. In this study, single‐cell RNA sequencing, spatial transcriptomics, and bulk ATAC‐sequence are integrated from a series of patients with PCa and healthy controls. A stemness subset of club cells marked with SOX9highARlow expression is identified, which is markedly enriched after neoadjuvant androgen‐deprivation therapy (ADT). Furthermore, a subset of CD8+CXCR6+ T cells that function as effector T cells is markedly reduced in patients with malignant PCa. For spatial transcriptome analysis, machine learning and computational intelligence are comprehensively utilized to identify the cellular diversity of prostate cancer cells and cell‐cell communication in situ. Macrophage and neutrophil state transitions along the trajectory of cancer progression are also examined. Finally, the immunosuppressive microenvironment in advanced PCa is found to be associated with the infiltration of regulatory T cells (Tregs), potentially induced by an FAP+ fibroblast subset. In summary, the cellular heterogeneity is delineated in the stage‐specific PCa microenvironment at single‐cell resolution, uncovering their reciprocal crosstalk with disease progression, which can be helpful in promoting PCa diagnosis and therapy.
Deficiency of Nuclear Receptor Coactivator 3 Aggravates Diabetic Kidney Disease by Impairing Podocyte Autophagy
Authors: Xie Yaru , Yuan Qian , Cao Xinyi , Qiu Yang , Zeng Jieyu , Cao Yiling , Xie Yajuan , Meng Xianfang , Huang Kun , Yi Fan , Zhang Chun
Published: March 2024

Nuclear receptors (NRs) are important transcriptional factors that mediate autophagy, preventing podocyte injury and the progression of diabetic kidney disease (DKD). However, the role of nuclear receptor coactivators that are powerful enhancers for the transcriptional activity of NRs in DKD remains unclear. In this study, a significant decrease in Nuclear Receptor Coactivator 3 (NCOA3) is observed in injured podocytes caused by high glucose treatment. Additionally, NCOA3 overexpression counteracts podocyte damage by improving autophagy. Further, Src family member, Fyn is identified to be the target of NCOA3 that mediates the podocyte autophagy process. Mechanistically, NCOA3 regulates the transcription of Fyn in a nuclear receptor, PPAR‐γ dependent way. Podocyte‐specific NCOA3 knockout aggravates albuminuria, glomerular sclerosis, podocyte injury, and autophagy in DKD mice. However, the Fyn inhibitor, AZD0530, rescues podocyte injury of NCOA3 knockout DKD mice. Renal NCOA3 overexpression with lentivirus can ameliorate podocyte damage and improve podocyte autophagy in DKD mice. Taken together, the findings highlight a novel target, NCOA3, that protects podocytes from high glucose injury by maintaining autophagy.
A Multi‐foci Sparse‐Aperture Metalens
Authors: Xu Borui , Wei Wei , Tang Ping , Shao Jingzhu , Zhao Xiangyu , Chen Bo , Dong Shengxiang , Wu Chongzhao
Published: March 2024

Multi‐foci lenses are essential components for optical communications, virtual reality display and microscopy, yet the bulkiness of conventional counterparts has significantly hindered their widespread applications. Benefiting from the unprecedented capability of metasurfaces in light modulation, metalenses are able to provide multi‐foci functionality with a more compact footprint. However, achieving imaging quality comparable to that of corresponding single‐foci metalenses at each focal point poses a challenge for existing multi‐foci metalenses. Here, a polarization‐independent all‐dielectric multi‐foci metalens is proposed and experimentally demonstrated by spatially integrating single‐foci optical sparse‐aperture sub‐metalenses. Such design enables the metalens to generate multiple focal points, while maintaining the ability to capture target information comparable to that of a single‐foci metalens. The proposed multi‐foci metalens is composed of square‐nanohole units array fabricated by two‐photon polymerization. The focusing characteristic and imaging capability are demonstrated upon the illumination of an unpolarized light beam. This work finds a novel route toward multi‐foci metalenses and may open a new avenue for dealing with the trade‐off between multi‐foci functionality and high‐quality imaging performance.
Neutrophil to lymphocyte ratio in captive olive baboons (Papio anubis): The effects of age, sex, rearing, stress, and pregnancy
Authors: Neal Sarah J. , Achorn Angela M. , Schapiro Steven J. , Hopkins William D. , Simmons Joe H.
Published: March 2024

In apes and humans, neutrophil to lymphocyte ratio (NLR) can be used as a predictive indicator of a variety of clinical conditions, longevity, and physiological stress. In chimpanzees specifically, NLR systematically varies with age, rearing, sex, and premature death, indicating that NLR may be a useful diagnostic tool in assessing primate health. To date, just one very recent study has investigated NLR in old world monkeys and found lower NLR in males and nursery‐reared individuals, as well as a negative relationship between NLR and disease outcomes. Given that baboons are increasingly used as research models, we aimed to characterize NLR in baboons by providing descriptive data and examinations of baboon NLR heritability, and of the relationships between NLR, age, rearing, and sex in 387 olive baboons (Papio anubis) between 6 months and 19 years of age. We found that (1) mother‐reared baboons had higher NLRs than nursery‐reared baboons; (2) females had higher NLRs than males; and (3) there was a quadratic relationship between NLR and age, such that middle‐aged individuals had the highest NLR values. We also examined NLR as a function of transport to a new facility using a subset of the data. Baboons exhibited significantly higher transport NLRs compared to routine exam NLRs. More specifically, adult baboons had higher transport NLRs than routine NLRs, whereas juveniles showed no such difference, suggesting that younger animals may experience transport stress differently than older animals. We also found that transport NLR was heritable, whereas routine NLR was not, possibly suggesting that stress responses (as indicated in NLR) have a strong genetic component. Consistent with research in humans and chimpanzees, these findings suggest that NLR varies with important biological and life history variables and that NLR may be a useful health biomarker in baboons.
Catalytic Ring Expanding Difluorination: An Enantioselective Platform to Access β,β‐Difluorinated Carbocycles
Authors: Ruyet Louise , Roblick Christoph , Häfliger Joel , Wang Zi‐Xuan , Stoffels Tobias Jürgen , Daniliuc Constantin G. , Gilmour Ryan
Published: March 2024

Cyclic β,β‐difluoro‐carbonyl compounds have a venerable history as drug discovery leads, but limitations in the synthesis arsenal continue to impede chemical space exploration. This challenge is particularly acute in the arena of fluorinated medium rings where installing the difluoromethylene unit subtly alters the ring conformation by expanding the internal angle (∠C−CF2−C>∠C−CH2−C): this provides a handle to modulate physicochemistry (e.g. pKa). To reconcile this disparity, a highly modular ring expansion has been devised that leverages simple α,β‐unsaturated esters and amides, and processes them to one‐carbon homologated rings with concomitant geminal difluorination (6 to 10 membered rings, up to 95 % yield). This process is a rare example of the formal difluorination of an internal alkene and is enabled by sequential I(III)‐enabled O‐activation. Validation of enantioselective catalysis in the generation of unprecedented medium ring scaffolds is reported (up to 93 : 7 e.r.) together with X‐ray structural analyses and product derivatization.
Construction of a hybrid flame retardant based on mesoporous silica for enhancing fire safety, smoke suppression, and mechanical properties of epoxy resins
Authors: Yue Liang , Shi Shuyang , Zheng Shuxian , Huang Yiwen , Rao Wenhui , Yu Chuanbai
Published: March 2024

In order to improve the fire safety of epoxy resins (EPs), the SBA‐15 based hybrid flame retardant (SNAZD) was synthesized via an organic–inorganic hybridization strategy of mesoporous silica SBA‐15. Relying on electrostatic interaction, the zinc amino‐tris‐(methylenephosphonate) (Zn‐ATMP) was successfully introduced into the pore channels of SBA‐15. Then, 9,10‐dihydro‐9‐oxa‐10‐phosphaphenanthrene‐10‐oxide (DOPO) was successfully loaded into the pores of SBA‐15 under vacuum. The results show that the EP composites with the 5%SNAZD sample (sample EP‐5%SNAZD) showed a LOI value of 30.9% and achieved the vertical burning V‐0 rating. In comparison to EP, the peak heat release rate, peak smoke production rate, and production rate of CO of EP‐3%SNAZD were reduced by 32.2%, 31.9%, and 20.0%, respectively. This is due to the presence of Si, P, N, and Zn elements in the SNAZD, which promoted the generation of a high yield of dense char residue and inhibited the release of toxic gasses. And the impact strength and flexural strength of EP‐1%SNAZD were increased by 19.5% and 15.6%, respectively, and the E' of EP‐5%SNAZD increased by 49.1% when compared with the neat EP. This work provides a general strategy for the design of mesoporous hybrid flame retardant and creates additional opportunities for applications of EP.
A comprehensive review on potential drug–drug interactions of proton pump inhibitors with antidiabetic drugs metformin and DPP‐4 inhibitors
Authors: Tasnim Jarin , Hashim Najihah Mohd , Han Heh Choon
Published: March 2024

A drug interaction is a condition in which two or more drugs are taken at the same time. Type 2 diabetes mellitus is a significant contributor to polypharmacy. Proton pump inhibitors (PPIs) are often prescribed in combination with metformin or DPP‐4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin) or a combined dose of metformin and DPP‐4 inhibitor to treat gastritis in diabetic patients. This review article mainly focused on evaluating the potential drug–drug interactions (DDIs) between PPIs (i.e. esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) with metformin and PPIs with DPP‐4 inhibitors. The findings demonstrated the existence of pharmacokinetic and pharmacodynamic DDIs between the aforementioned PPIs with metformin and DPP‐4 inhibitors, which could impact the biological activities (i.e., hypoglycemia) of these drugs. Moreover, this review suggested that esomeprazole could be the best drug in the PPI group to be prescribed simultaneously with metformin and DPP‐4 inhibitors, as most of the antidiabetic drugs of this study did not show any interaction with esomeprazole. The findings of this study also revealed that both antidiabetic drugs and PPIs could have positive interactions as PPIs have the potential to lessen the gastrointestinal side effects of metformin and DPP‐4 inhibitors. To achieve the greatest therapeutic impact with the fewest side effects, careful dose control of these drugs is required. So, more extensive research on both human and animal subjects are needed to ascertain the veracity of this hypothesis.
Paynantheine more effectively reverses multidrug resistance in malignant EPG85.257RDB and MCF7MX cells than morphine and speciociliatine
Authors: Abdali Nayereh , Nadipour Borujeni Mohammad , Hosseini Sayedeh Azimeh , Malekzadeh Rahim , Abolhasani Marzieh , Mirzaei Seyed Abbas , Elahian Fatemeh
Published: March 2024

The possible interactions of morphine, paynantheine and speciociliatine alkaloids with ATP‐binding cassette (ABC) transporters was investigated. The compounds were docked against ABCG2 and ABCB1 to predict the binding mode of alkaloids in active binding sites. The cytotoxicity of morphine, paynantheine and speciociliatine for EPG85.257RDB and MCF7MX cells was determined and ABCB1 and ABCG2 gene and protein expression were determined. The binding score of paynantheine to ABCB1 was higher in the docking studies. Paynantheine and speciociliatine had similar binding scores to ABCB1, but higher binding scores to ABCG2 than did morphine. Paynantheine and speciociliatine were more effective against MCF7MX and EPG85.257RDB cells and showed greater cyctotoxicity in the MTT assay. The effect of morphine and paynantheine on the ABCB1 gene and protein expression suggests these compounds can reduce resistance in cancer patients, but that speciociliatine may not be a suitable candidate because of its increased ABCB1 expression while speciociliatine decreased the expression of ABCG2 in MCF7MX cells. This indicates that speciociliatine is a better candidate for reducing drug resistance in this cell line. Structural modification, drug‐metabolizing enzymes and differences in the binding sites could cause functional differences between these compounds.
Use of Suspended Particles as a New Approach to Increase the Active Electrode Area in Water Electrolysis Experiments
Authors: Balkenhohl Danni , Huck Marten , Bookholt Tom , Lilli Bettina , Enke Dirk , Rüwe Klara , Brune Julia , Daum Diemo , Schäfer Helmut
Published: March 2024

The development of base metal electrodes that can act as active and stable oxygen generating electrodes in water electrolysis systems, especially at low pH levels, remains a challenge. The use of suspensions as electrolytes for water splitting has until recently been limited to photoelectrocatalytic approaches. A high current density (j=30 mA/cm2) for water electrolysis has been achieved at a very low oxygen evolution reaction (OER) potential (E=1.36 V vs. RHE) using a SnO2/H2SO4 suspension–based electrolyte in combination with a steel anode. More importantly, the high charge–to–oxygen conversion rate (Faraday efficiency of 88 % for OER at j=10 mA/cm2 current density). Since cyclic voltammetry (CV) experiments show that oxygen evolution starts at a low, but not exceptionally low, potential, the reason for the low potential in chronoamperometry (CP) tests is an increase in the active electrode area, which has been confirmed by various experiments. For the first time, the addition of a relatively small amount of solids to a clear electrolyte has been shown to significantly reduce the overpotential of the OER in water electrolysis down to the 100 mV region, resulting in a remarkable reduction in anode wear while maintaining a high current density.
Breaking the Rules: On the Relative Stability of Some Methylencyclopropane and Methylcyclopropene Derivatives
Authors: Santalucia Delio , Bondanza Mattia , Lipparini Filippo , Ripszam Matyas , Rossi Nicolò , Mandoli. Alessandro
Published: March 2024

The structure of the spirocyclic product obtained by reacting catechol with 1,1‐dichloro‐2‐(chloromethyl)cyclopropane is shown by NMR and X‐ray analysis to be that of a 2‐methylcyclopropene (MeCP), instead of the previously reported 2‐methylenecyclopropane (MCP) one. The study of the equilibration between the two isomeric forms by experimental and computational means (including both Density Functional Theory – DFT – and Coupled Cluster with single, double, and perturbative triple excitations – CCSD(T) – calculations) revealed that, at variance with most of the alkylidenecyclopropane/alkylcyclopropene systems described to date, for the compounds of the present study the MeCP derivative is more stable by≈ 2.5–3.0 Kcal mol−1 than the MCP one. The extension of the DFT and CCSD(T) study to other spiro‐MCP/MeCP pairs suggests that the origin of the unexpected shift of the equilibrium position can be tracked back to a combination of electronic and ring‐strain effects. These findings lead to re‐think a long‐standing, and substantially undisputed belief in the area of unsaturated cyclopropane derivatives.
Covalent and Visible‐Light Photoswitchable Derivatives of the Potent Synthetic Opioid Isotonitazene and Other Nitazenes
Authors: Lahmy Ranit , Hübner Harald , Gmeiner Peter , König Burkhard
Published: March 2024

Isotonitazene belongs to a potent class of μ‐opioid receptor (μOR) ligands, known as nitazenes. The lack of knowledge surrounding this agonist and others in its class has sparked thorough re‐investigations. To aid in these investigations, the purportedly covalent yet underexplored nitazene BIT was biochemically re‐evaluated in this work, along with a newly synthesized analogue, Iso‐BIT. Moreover, in the pursuit of understanding the mechanism, function and interactions of the μOR, this study involved developing photoswitchable nitazene derivatives as potential probe molecules. Converting known ligands into azo‐containing photoswitchable derivatives offers the opportunity to modulate ligand structure with light, allowing for photocontrol of compound activity. While photocontrol of μOR activity could not be entirely achieved, photophysical evaluation of these 2‐benzimidazole azo‐arenes revealed a novel photoswitch scaffold that responds to visible light. Furthermore, azo‐containing 2 e and 3 e emerged as promising nitazene derivatives that were able to form an exceptionally high fraction of covalent‐ligand receptor complexes with wild‐type μOR at physiological pH.
Discover how a shared vision can become a guiding star
Authors: Freebairn‐Smith Laura , Kitayama Jason
Published: March 2024

Visionary leaders and leaders for the twenty‐first century and for the millennium need to change their own organizations, activating the energy of their internal cultures to achieve big goals for the four Ps (planet, people, profit, and purpose).
Conducting polymer hydrogels based on supramolecular strategies for wearable sensors
Authors: Sun Zhiyuan , Ou Qingdong , Dong Chao , Zhou Jinsheng , Hu Huiyuan , Li Chong , Huang Zhandong
Published: March 2024

Conductive polymer hydrogels (CPHs) are gaining considerable attention in developing wearable electronics due to their unique combination of high conductivity and softness. However, in the absence of interactions, the incompatibility between hydrophobic conductive polymers (CPs) and hydrophilic polymer networks gives rise to inadequate bonding between CPs and hydrogel matrices, thereby significantly impairing the mechanical and electrical properties of CPHs and constraining their utility in wearable electronic sensors. Therefore, to endow CPHs with good performance, it is necessary to ensure a stable and robust combination between the hydrogel network and CPs. Encouragingly, recent research has demonstrated that incorporating supramolecular interactions into CPHs enhances the polymer network interaction, improving overall CPH performance. However, a comprehensive review focusing on supramolecular CPH (SCPH) for wearable sensing applications is currently lacking. This review provides a summary of the typical supramolecular strategies employed in the development of high‐performance CPHs and elucidates the properties of SCPHs that are closely associated with wearable sensors. Moreover, the review discusses the fabrication methods and classification of SCPH sensors, while also exploring the latest application scenarios for SCPH wearable sensors. Finally, it discusses the challenges of SCPH sensors and offers suggestions for future advancements.
Design and synthesis of APN and 3CLpro dual‐target inhibitors based on STSBPT with anticoronavirus activity
Authors: Zheng Youle , Feng Jin , Song Yanbin , Yu Yixin , Ling Min , Zhang Mengjia , Xie Haijiao , Li Wentao , Xu Wang
Published: March 2024

Coronaviruses (CoVs) have continuously posed a threat to human and animal health. However, existing antiviral drugs are still insufficient in overcoming the challenges caused by multiple strains of CoVs. And methods for developing multi‐target drugs are limited in terms of exploring drug targets with similar functions or structures. In this study, four rounds of structural design and modification on salinomycin were performed for novel antiviral compounds. It was based on the strategy of similar topological structure binding properties of protein targets (STSBPT), resulting in the high‐efficient synthesis of the optimal compound M1, which could bind to aminopeptidase N and 3C‐like protease from hosts and viruses, respectively, and exhibit a broad‐spectrum antiviral effect against severe acute respiratory syndrome CoV 2 pseudovirus, porcine epidemic diarrhea virus, transmissible gastroenteritis virus, feline infectious peritonitis virus and mouse hepatitis virus. Furthermore, the drug‐binding domains of these proteins were found to be structurally similar based on the STSBPT strategy. The compounds screened and designed based on this region were expected to have broad‐spectrum and strong antiviral activities. The STSBPT strategy is expected to be a fundamental tool in accelerating the discovery of multiple targets with similar effects and drugs.
Interpreting biogeochemical processes through the relationship between total alkalinity and dissolved inorganic carbon: Theoretical basis and limitations
Authors: Yin Hang , Jin Lei , Hu Xinping
Published: March 2024

The marine carbonate system is influenced by anthropogenic CO2 uptake, biogeochemical processes, and physical changes that involve freshwater input and removal. Two frequently used parameters to quantify seawater carbonate system are total alkalinity (TA) and total dissolved inorganic carbon (DIC). To account for the physical changes, both TA and DIC are usually normalized to a reference salinity (i.e., nTA and nDIC), and then the relationship between nTA and nDIC is used to identify major biogeochemical processes that regulate the carbonate system, based on process‐specific reaction stoichiometry. However, the theoretical basis of this interpretation has not been holistically examined. In this study, we validated this method under  idealized conditions and discussed the associated assumptions and limitations. Furthermore, we applied this method to interpret field TA and DIC data from a lagoonal estuary in the northwestern Gulf of Mexico. Our results demonstrated that evaluating field data that encompass multiple stations and time periods could be problematic. In addition, various combinations of biogeochemical processes can lead to the same nTA–nDIC relationship, even though the relative importance of each individual process may vary significantly. Therefore, the stoichiometric relationship relying solely on TA and DIC data is not a definitive approach for uncovering dominant biogeochemical processes. Instead, measurements of process‐specific parameters are necessary.
Accurate determination of sorghum origin based on hyperspectral imaging technology and machine learning
Authors: Zhao Guangxia , Wang Qi , Zhang Pengfei , Xu Zhuopin , Tang Liwen , Li Xiaohong
Published: March 2024

Sorghum is an important crop, and the quality of sorghum of the same variety from different geographic origins varies greatly. This study focuses on HongYingZi sorghum from five distinct origins, employing a combination of hyperspectral imaging (HSI) technology and machine learning algorithms to investigate methods for classifying sorghum origin. Multiplicative scatter correction and the Savizkg‐Golay algorithms were used to preprocess HSI data, and the characteristic wavelengths were screened by the successive projections algorithm (SPA). Based on AdaBoost, ExtraTreesClassifier, Gradient Boosting, Decision Tree, and Random Forest algorithms, classification models based hyperspectral data were established respectively, and validation experiments were conducted. The results show that for the full‐band spectra, the ExtraTreesClassifier algorithm has the highest accuracy; the average accuracy on the training set and test set were 0.9925 and 0.9854, respectively. The classification results were visualized and analyzed using Python. The results highlight the effectiveness of HSI combined with machine learning algorithms in achieving nondestructive detection of sorghum origin within the same variety. This study provides a precise method for rapid and nondestructive determination of sorghum origin.