bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormonal Cycle Modulates Arousal Circuitry in Women Using Functional Magnetic Resonance Imaging
Authors: Goldstein Jill M. , Jerram Matthew , Poldrack Russell , Ahern Todd , Kennedy David N. , Seidman Larry J. , Makris Nikos
Published: October 2005

Sex-specific behaviors are in part based on hormonal regulation of brain physiology. This functional magnetic resonance imaging (fMRI) study demonstrated significant differences in activation of hypothalamic-pituitary-adrenal (HPA) circuitry in adult women with attenuation during ovulation and increased activation during early follicular phase. Twelve normal premenopausal women were scanned twice during the early follicular menstrual cycle phase compared with late follicular/midcycle, using negative valence/high arousal versus neutral visual stimuli, validated by concomitant electrodermal activity (EDA). Significantly greater magnitude of blood oxygenation level-dependent signal changes were found during early follicular compared with midcycle timing in central amygdala, paraventricular and ventromedial hypothalamic nuclei, hippocampus, orbitofrontal cortex (OFC), anterior cingulate gyrus (aCING), and peripeduncular nucleus of the brainstem, a network of regions implicated in the stress response. Arousal (EDA) correlated positively with brain activity in amygdala, OFC, and aCING during midcycle but not in early follicular, suggesting less cortical control of amygdala during early follicular, when arousal was increased. This is the first evidence suggesting that estrogen may likely attenuate arousal in women via cortical-subcortical control within HPA circuitry. Findings have important implications for normal sex-specific physiological functioning and may contribute to understanding higher rates of mood and anxiety disorders in women and differential sensitivity to trauma than men.
Early Experience Modifies the Postnatal Assembly of Autonomic Emotional Motor Circuits in Rats
Authors: Card J. Patrick , Levitt Pat , Gluhovsky Maxim , Rinaman Linda
Published: October 2005

Rat pups that are repeatedly handled and separated from their dam exhibit altered adult behavioral, endocrine, and autonomic responses to stress, but the extent to which early handling and/or maternal separation (H/S) alters the development of circuits that underlie these responses is unknown. The present study tested the hypothesis that early H/S alters the postnatal assembly of synapses within preautonomic emotional motor circuits. Circuit development was traced by synapse-dependent retrograde transneuronal transport of pseudorabies virus (PRV) from the stomach wall. Control and H/S rats were analyzed between postnatal day 6 (P6) and P10, a period of rapid synaptic assembly among preautonomic circuit components. Pups in H/S groups were removed from their dam daily for either 15 min or 3 h beginning on P1, and were injected with virus on P8 and perfused on P10. Quantitative analyses of primary and transsynaptic PRV immunolabeling confirmed an age-dependent assembly of hypothalamic, limbic, and cortical inputs to autonomic nuclei. Circuit assembly was significantly altered in H/S pups, in which fewer neurons in the central amygdala, the bed nucleus of the stria terminalis, and visceral cortices were infected compared with age-matched controls. In contrast, H/S did not alter the assembly of paraventricular hypothalamic inputs to gastric autonomic neurons. H/S-related reductions in limbic and cortical transneuronal infection were similar in pups exposed daily to 15 min or 3 h maternal separation. These findings support the view that environmental events during early postnatal life can influence the formation of neural circuits that provide limbic and cortical control over autonomic emotional motor output.
Differential Expression of TASK Channels between Horizontal Interneurons and Pyramidal Cells of Rat Hippocampus
Authors: Taverna Stefano , Tkatch Tatiana , Metz Alexia E. , Martina Marco
Published: October 2005

Among the electrophysiological properties differentiating stratum oriens horizontal interneurons from pyramidal neurons of the CA1 hippocampal subfield are the more depolarized resting potential and the higher input resistance; additionally, these interneurons are also less sensitive to ischemic damage than pyramidal cells. A differential expression of pH-sensitive leakage potassium channels (TASK) could contribute to all of these differences. To test this hypothesis, we studied the expression and properties of TASK channels in the two cell types.

Electrophysiological recordings from acute slices showed that barium- and bupivacaine-sensitive TASK currents were detectable in pyramidal cells but not in interneurons and that extracellular acidification caused a much stronger depolarization in pyramidal cells than in interneurons. This pyramidal cell depolarization was paralleled by an increase of the input resistance, suggesting the blockade of a background conductance.

Single-cell reverse transcription-PCR experiments showed that the expression profile of TASK channels differ between the two cell types and suggested that these channels mediate an important share of the leakage current of pyramidal cells.

We suggest that the different expression of TASK channels in these cell types contribute to their electrophysiological differences and may result in cell-specific sensitivity to extracellular acidification in conditions such as epilepsy and ischemia.
Visual Prey Capture in Larval Zebrafish Is Controlled by Identified Reticulospinal Neurons Downstream of the Tectum
Authors: Gahtan Ethan , Tanger Paul , Baier Herwig
Published: October 2005

Many vertebrates are efficient hunters and recognize their prey by innate neural mechanisms. During prey capture, the internal representation of the prey's location must be constantly updated and made available to premotor neurons that convey the information to spinal motor circuits. We studied the neural substrate of this specialized visuomotor system using high-speed video recordings of larval zebrafish and laser ablations of candidate brain structures. Seven-day-old zebrafish oriented toward, chased, and consumed paramecia with high accuracy. Lesions of the retinotectal neuropil primarily abolished orienting movements toward the prey. Wild-type fish tested in darkness, as well as blind mutants, were impaired similarly to tectum-ablated animals, suggesting that prey capture is mainly visually mediated. To trace the pathway further, we examined the role of two pairs of identified reticulospinal neurons, MeLc and MeLr, located in the nucleus of the medial longitudinal fasciculus of the tegmentum. These two neurons extend dendrites into the ipsilateral tectum and project axons into the spinal cord. Ablating MeLc and MeLr bilaterally impaired prey capture but spared several other behaviors. Ablating different sets of reticulospinal neurons did not impair prey capture, suggesting a selective function of MeLr and MeLc in this behavior. Ablating MeLc and MeLr neurons unilaterally in conjunction with the contralateral tectum also mostly abolished prey capture, but ablating them together with the ipsilateral tectum had a much smaller effect. These results suggest that MeLc and MeLr function in series with the tectum, as part of a circuit that coordinates prey capture movements.
Circadian Regulation and Function of Voltage-Dependent Calcium Channels in the Suprachiasmatic Nucleus
Authors: Nahm Sang-Soep , Farnell Yuhua Z. , Griffith William , Earnest David J.
Published: October 2005

Individual neurons within the suprachiasmatic nuclei (SCNs) are capable of functioning as autonomous clocks and generating circadian rhythms in the expression of genes that form the molecular clockworks. Limited information is available on how these molecular oscillations in individual clock cells are coordinated to provide for the ensemble rhythmicity that is normally observed from the entire SCN. Because calcium influx via voltage-dependent calcium channels (VDCCs) has been implicated in the regulation of gene expression and synchronization of rhythmicity across the population of SCN clock cells, we first examined the rat SCN and an immortalized line of SCN cells (SCN2.2) for expression and circadian regulation of different VDCC α1 subunits. The rat SCN and SCN2.2 cells exhibited mRNA expression for all major types of VDCC α1 subunits. Relative levels of VDCC expression in the rat SCN and SCN2.2 cells were greatest for L-type channels, moderate for P/Q- and T-type channels, and minimal for R- and N-type channels. Interestingly, both rat SCN and SCN2.2 cells showed rhythmic expression of P/Q- and T-type channels. VDCC involvement in the regulation of molecular rhythmicity in SCN2.2 cells was then examined using the nonselective antagonist, cadmium. The oscillatory patterns ofrPer2andrBmal1expression were abolished in cadmium-treated SCN2.2 cells without affecting cellular morphology and viability. These findings raise the possibility that the circadian regulation of VDCC activity may play an important role in maintaining rhythmic clock gene expression across an ensemble of SCN oscillators.
CHIP Suppresses Polyglutamine Aggregation and ToxicityIn VitroandIn Vivo
Authors: Miller Victor M. , Nelson Rick F. , Gouvion Cynthia M. , Williams Aislinn , Rodriguez-Lebron Edgardo , Harper Scott Q. , Davidson Beverly L. , Rebagliati Michael R. , Paulson Henry L.
Published: October 2005

Huntington's disease (HD) and other polyglutamine (polyQ) neurodegenerative diseases are characterized by neuronal accumulation of the disease protein, suggesting that the cellular ability to handle abnormal proteins is compromised. As both a cochaperone and ubiquitin ligase, the C-terminal Hsp70 (heat shock protein 70)-interacting protein (CHIP) links the two major arms of protein quality control, molecular chaperones, and the ubiquitin-proteasome system. Here, we demonstrate that CHIP suppresses polyQ aggregation and toxicity in transfected cell lines, primary neurons, and a novel zebrafish model of disease. Suppression by CHIP requires its cochaperone function, suggesting that CHIP acts to facilitate the solubility of mutant polyQ proteins through its interactions with chaperones. Conversely, HD transgenic mice that are haploinsufficient for CHIP display a markedly accelerated disease phenotype. We conclude that CHIP is a critical mediator of the neuronal response to misfolded polyQ protein and represents a potential therapeutic target in this important class of neurodegenerative diseases.
Cholinergic Modulation of Vibrissal Receptive Fields in Trigeminal Nuclei
Authors: Timofeeva Elena , Dufresne Caroline , Sík Attila , Zhang Zhong-Wei , Deschênes Martin
Published: October 2005

In sensory systems, it is usually considered that mesopontine cholinergic neurons exert their modulatory action in the thalamus by enhancing the relay of sensory messages during states of neural network desynchronization. Here, we report a projection heretofore unknown of these cholinergic cells to the interpolar division of the brainstem trigeminal complex in rats. After FluoroGold injection in the interpolar nucleus, a number of retrogradely labeled cells were found bilaterally in the pedunculopontine tegmental nucleus, and immunostaining revealed that the vast majority of these cells were also positive for choline acetyltransferase. Immunostaining for the acetylcholine vesicular transporter confirmed the presence of cholinergic terminals in the interpolar nucleus, where electron microscopy showed that they make symmetric and asymmetric synaptic contacts with dendrites and axon terminals. In agreement with these anatomical data, recordings in slices showed that the cholinergic agonist carbachol depolarizes large-sized interpolaris cells and increases their excitability. Local application of carbacholin vivoenhances responses to adjacent whiskers, whereas systemic administration of the cholinergic antagonist scopolamine produces an opposite effect. Together, these results show that mesopontine cholinergic neurons exert a direct, effective control over receptive field size at the very first relay stations of the vibrissal system in rodents. As far as receptive field synthesis in the lemniscal pathway relies on intersubnuclear projections from the spinal complex, it follows that cholinergic modulation of sensory transmission in the interpolar nucleus will have a direct bearing on the type of messages that is forwarded to the thalamus and cerebral cortex.
FDA Adds Boxed Warning to CAR T-Cell Therapies, but Says Benefits Outweigh Risks of Secondary Cancers
Authors: Suran Melissa
Published: February 2024

This Medical News article discusses the US Food and Drug Administration’s new boxed warning requirement and investigation of secondary malignancies after CAR T-cell therapy.
Interventions for Optimization of Guideline-Directed Medical Therapy
Authors: Tang Amber B. , Brownell Nicholas K. , Roberts Jacob S. , Haidar Amier , Osuna-Garcia Antonia , Cho David J. , Bokhoor Pooya , Fonarow Gregg C.
Published: February 2024

Importance

Implementation of guideline-directed medical therapy (GDMT) in real-world practice remains suboptimal. It is unclear which interventions are most effective at addressing current barriers to GDMT in patients with heart failure with reduced ejection fraction (HFrEF).

Objective

To perform a systematic review to identify which types of system-level initiatives are most effective at improving GDMT use among patients with HFrEF.

Evidence Review

PubMed, Embase, Cochrane, CINAHL, and Web of Science databases were queried from January 2010 to November 2023 for randomized clinical trials that implemented a quality improvement intervention with GDMT use as a primary or secondary outcome. References from related review articles were also included for screening. Quality of studies and bias assessment were graded based on the Cochrane Risk of Bias tool and Oxford Centre for Evidence-Based Medicine.

Findings

Twenty-eight randomized clinical trials were included with an aggregate sample size of 19 840 patients. Studies were broadly categorized as interdisciplinary interventions (n = 15), clinician education (n = 5), electronic health record initiatives (n = 6), or patient education (n = 2). Overall, interdisciplinary titration clinics were associated with significant increases in the proportion of patients on target doses of GDMT with a 10% to 60% and 2% to 53% greater proportion of patients on target doses of β-blockers and renin-angiotensin-aldosterone system inhibitors, respectively, in intervention groups compared with usual care. Other interventions, such as audits, clinician and patient education, or electronic health record alerts, were also associated with some improvements in GDMT utilization, though these findings were inconsistent across studies.

Conclusions and Relevance

This review summarizes interventions aimed at optimization of GDMT in clinical practice. Initiatives that used interdisciplinary teams, largely comprised of nurses and pharmacists, most consistently led to improvements in GDMT. Additional large, randomized studies are necessary to better understand other types of interventions, as well as their long-term efficacy and sustainability.
Racial and Ethnic Disparities in Patient Restraint in Emergency Departments by Police Transport Status
Authors: Chang-Sing Erika , Smith Colin M. , Gagliardi Jane P. , Cramer Laura D. , Robinson Leah , Shah Dhruvil , Brinker Morgan , Jivalagian Patelle , Hu Yue , Turner Nicholas A. , Wong Ambrose H.
Published: February 2024

Importance

Black patients are more likely than White patients to be restrained during behavioral crises in emergency departments (EDs). Although the perils of policing mental health for Black individuals are recognized, it is unclear whether or to what extent police transport mediates the association between Black race and use of physical restraint in EDs.

Objective

To evaluate the degree to which police transport mediates the association between Black race and use of physical restraint in EDs.

Design, Setting, and Participants

This retrospective, cross-sectional study used electronic health record data from ED visits by adults (aged ≥18 years) to 3 hospitals in the southeastern US and 10 in the northeastern US between January 1, 2015, and December 31, 2022. Data were analyzed from September 1, 2022, to May 30, 2023.

Exposures

Race, ethnicity, and police transport to the hospital.

Main Outcomes and Measures

The primary outcome variable was the presence of an order for restraints during an ED visit.

Results

A total of 4 263 437 ED visits by 1 257 339 patients (55.5% of visits by female and 44.5% by male patients; 26.1% by patients 65 years or older) were included in the study. Black patients accounted for 27.5% of visits; Hispanic patients, 17.6%; White patients, 50.3%; and other or unknown race or ethnicity, 4.6%. In models adjusted for age, sex, site, previous behavioral or psychiatric history, and visit diagnoses, Black patients were at increased odds of experiencing restraint compared with White patients (adjusted odds ratio [AOR], 1.33 [95% CI, 1.28-1.37]). Within the mediation analysis, Black patients had higher odds of being brought to the hospital by police compared with all other patients (AOR, 1.38 [95% CI, 1.34-1.42]). Patients brought to the ED under police transport had increased odds of experiencing restraint compared with all other modes of transport (AOR, 5.51 [95% CI, 5.21-5.82]). The estimated proportion of use of restraints for Black patients mediated by police transport was 10.70% (95% CI, 9.26%-12.53%).

Conclusions and Relevance

In this cross-sectional study of ED visits across 13 hospitals, police transport may have mediated the association between Black race and use of physical restraint. These findings suggest a need to further explore the mechanisms by which transport to emergency care may influence disparate restrictive interventions for patients experiencing behavioral emergencies.
Lifetime Suicide Attempts in Otherwise Psychiatrically Healthy Individuals
Authors: Oquendo Maria A. , Wall Melanie , Wang Shuai , Olfson Mark , Blanco Carlos
Published: February 2024

Importance

Not all people who die by suicide have a psychiatric diagnosis; yet, little is known about the percentage and demographics of individuals with lifetime suicide attempts who are apparently psychiatrically healthy. If such suicide attempts are common, there are implications for suicide risk screening, research, policy, and nosology.

Objective

To estimate the percentage of people with lifetime suicide attempts whose first attempt occurred prior to onset of any psychiatric disorder.

Design, Setting, and Participants

This cross-sectional study used data from the US National Epidemiologic Study of Addictions and Related Conditions III (NESARC-III), a cross-sectional face-to-face survey conducted with a nationally representative sample of the US civilian noninstitutionalized population, and included persons with lifetime suicide attempts who were aged 20 to 65 years at survey administration (April 2012 to June 2013). Data from the NESARC, Wave 2 survey from August 2004 to September 2005 were used for replication. Analyses were performed from April to August 2023.

Exposure

Lifetime suicide attempts.

Main Outcomes and Measures

The main outcome was presence or absence of a psychiatric disorder before the first lifetime suicide attempt. Among persons with lifetime suicide attempts, the percentage and 95% CI of those whose first suicide attempt occurred before the onset of any apparent psychiatric disorders was calculated, weighted by NESARC sampling and nonresponse weights. Separate analyses were performed for males, females, and 3 age groups (20 to <35, 35-50, and >50 to 65 years).

Results

In the total sample of 36 309 respondents, 1948 persons had lifetime suicide attempts; 66.8% (95% CI, 64.1%-69.4%) were female, and 6.2% (95% CI, 4.9%-7.4%) had no apparent lifetime psychiatric diagnoses when surveyed. In addition, 13.4% (95% CI, 11.6%-15.2%) made their first suicide attempt prior to psychiatric disorder onset. Thus, an estimated 19.6% of respondents first attempted suicide without an antecedent psychiatric disorder. No significant age or sex differences were detected in the percentage of those with lifetime suicide attempts absent psychiatric disorders, although females were more likely than males to attempt suicide in the year of psychiatric disorder onset (14.9% [95% CI, 12.5%-17.3%] vs 8.6% [95% CI, 6.0%-11.2%]; P < .001), and attempts were less frequent among those older than 50 to 65 years (3.9% [95% CI, 3.5%-4.4%] vs 6.1% [95% CI, 5.4%-6.8%] for 35-50 years and 6.2% [95% CI, 5.6%-6.9%] for 20 to <35 years; P < .001).

Conclusions and Relevance

In this study, an estimated 19.6% of individuals who attempted suicide did so despite not meeting criteria for an antecedent psychiatric disorder. This finding challenges clinical notions of who is at risk for suicidal behavior and raises questions about the safety of limiting suicide risk screening to psychiatric populations.
Electric Bicycle Injuries and Hospitalizations
Authors: Fernandez Adrian M. , Li Kevin D. , Patel Hiren V. , Allen Isabel Elaine , Ghaffar Umar , Hakam Nizar , Breyer Benjamin N.
Published: February 2024

This cross-sectional study investigates injury trends associated with electric bicycles in the US from 2017 to 2022.
Total Neoadjuvant Therapy With PD-1 Blockade for High-Risk Proficient Mismatch Repair Rectal Cancer
Authors: Li Yingjie , Pan Chaohu , Gao Yuye , Zhang Li , Ji Dengbo , Cui Xiaoli , Zhang Xiaoyan , Cai Yong , Zhang Yangzi , Yao Yunfeng , Wang Lin , Leng Jiahua , Zhan Tiancheng , Wu Dongfang , Gao Zhibo , Sun Ying-Shi , Li Zhongwu , Luo Haitao , Wu Aiwen
Published: February 2024

Importance

Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer, especially for patients with high-risk factors. However, the efficacy of TNT combined with immunotherapy for patients with proficient mismatch repair (pMMR) rectal cancer is unknown.

Objectives

To evaluate the safety and efficacy of TNT with induction chemoimmunotherapy followed by long-course chemoradiation in patients with high-risk, pMMR rectal cancer and to identify potential molecular biomarkers associated with treatment efficacy.

Design, Setting, and Participants

This cohort study was a single-arm phase 2 trial conducted at Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, from June 2020 to October 2021. Biopsies and plasma were collected before treatment for whole-exome sequencing and cell-free DNA sequencing, respectively. Data were analyzed from May 2022 to September 2022.

Interventions

Participants received 3 cycles of induction oxaliplatin and capecitabine combined with camrelizumab and radiotherapy (50.6 Gy in 22 fractions) with concurrent capecitabine. Patients without disease progression received 2 cycles of consolidation oxaliplatin/capecitabine.

Main Outcomes and Measures

The primary end point was pathologic complete response rate.

Results

Of 25 patients enrolled (19 men [76%]; 6 women [24%]; median [IQR] age, 58 [48-64] years), 22 patients (88%) completed the TNT schedule. The pathologic complete response rate was 33.3% (7/21). Twelve patients (48%) achieved clinical complete response, and 4 patients (16%) chose to watch and wait. R0 resection was achieved in 21 of 21 patients, and the major pathologic response rate was 38.1% (8/21). The most common adverse event was nausea (80%, 20/25); grade 3 toxic effects occurred in 9 of 25 patients (36%). Patients with tumor shrinkage of 50% or greater after induction oxaliplatin/capecitabine and camrelizumab or clinical complete response had higher percentages of LRP1B mutation. Mutation of LRP1B was associated with high tumor mutation burden and tumor neoantigen burden. Patients with high tumor mutation burden all benefited from therapy.

Conclusions and Relevance

This study found that TNT with induction chemoimmunotherapy followed by long-course chemoradiation was safe and effective for patients with high-risk rectal cancer with pMMR status. Longer follow-up and larger clinical studies are needed to validate this innovative regimen. There is also an urgent need to further validate the predictive value of LRP1B and discover other novel biomarkers with potential predictive value for rectal cancer.
Immunosuppressive role of BDNF in therapy‐induced neuroendocrine prostate cancer
Authors: Liu Yen‐Nien , Chen Wei‐Yu , Liu Ming‐Kun , Yeh Hsiu‐Lien , Chen Wei‐Hao , Jiang Kuo‐Ching , Li Han‐Ru , Chen Zi‐Qing , Wang Wan‐Hsin , Abou‐Kheir Wassim , Wen Yu‐Ching
Published: February 2024

Prostate stromal cells play a crucial role in the promotion of tumor growth and immune evasion in the tumor microenvironment (TME) through intricate molecular alterations in their interaction with prostate cancer (PCa) cells. While the impact of these cells on establishing an immunosuppressive response and influencing PCa aggressiveness remains incompletely understood. Our study shows that the activation of the leukemia inhibitory factor (LIF)/LIF receptor (LIFR) pathway in both prostate tumor and stromal cells, following androgen deprivation therapy (ADT), leads to the development of an immunosuppressive TME. Activation of LIF/LIFR signaling in PCa cells induces neuroendocrine differentiation (NED) and upregulates immune checkpoint expression. Inhibition of LIF/LIFR attenuates these effects, underscoring the crucial role of LIF/LIFR in linking NED to immunosuppression. Prostate stromal cells expressing LIFR contribute to NED and immunosuppressive marker abundance in PCa cells, while LIFR knockdown in prostate stromal cells reverses these effects. ADT‐driven LIF/LIFR signaling induces brain‐derived neurotrophic factor (BDNF) expression, which, in turn, promotes NED, aggressiveness, and immune evasion in PCa cells. Clinical analyses demonstrate elevated BDNF levels in metastatic castration‐resistant PCa (CRPC) and a positive correlation with programmed death‐ligand 1 (PDL1) and immunosuppressive signatures. This study shows that the crosstalk between PCa cells and prostate stromal cells enhances LIF/LIFR signaling, contributing to an immunosuppressive TME and NED in PCa cells through the upregulation of BDNF.
Effects of differences in facility types on occurrence of COVID‐19 cases and response after testing positive in nursing homes for the elderly: Case study on Kyoto City
Authors: Suzuki Kenji
Published: February 2024

The outbreak of COVID‐19 became a major problem at various facilities, and aged‐care facilities were no exception. In the event of a person detected positive for the disease, outpatient facilities were suspended, but inpatient facilities could not be suspended, and it became necessary to deal with the residents and positive people. This study aimed to obtain knowledge that would lead to the prevention of the spread of COVID‐19. The effects of differences in facility types were first examined on the occurrence of COVID‐19 cases and then on the response after testing positive in nursing homes for the elderly.
Ball‐Milling Synthesis of Richly Oxygenated Graphene‐Like Nanoplatelets from used Lithium Ion Batteries and Its Application for High Performance Sodium Ion Battery Anode
Authors: Zhang Jiakui , Lei Yu , Zhou Lingyun , Chen Xianghong , Huang Shuhan , Liu Liang , Liu Huakun , Dou Shixue , Xu Jiantie
Published: February 2024

The exploration of waste graphite from used lithium ion batteries (LIBs) and its derivatives for versatile applications is an efficient route to promote the environmental and eco‐friendly recycling of used LIBs. Sodium ion batteries (SIBs) are alternative candidates to LIBs mainly due to similar electrochemical mechanism of SIBs to LIBs and rich natural resource of Na. Herein, a holey waste graphite (hGw) with well‐defined porous structure is produced by the annealing of lithiated waste graphite (Li/Gw) from used LIBs under a flow gas of H2O and subsequent lithium leaching in DI water. Benefiting from the holey structure of hGw, holey graphene nanoplatelets (hGnw) with ultrahigh‐level edge‐grafted oxygen groups (≈37.8 at%) are synthesized by mechanical balling of hGw. As anode for SIBs, the hGnw present outstanding sodium ion storage properties with high initial Coulombic efficiency of 82.4%, high reversible capacity (e.g., 416.1 mAh g−1 at 0.03 A g−1), excellent rate capability (e.g., 153.3 mAh g−1 at 2 A g−1), and long‐term cycling stability (e.g., 152.7 mAh g−1 after 400 cycles at 1.5 A g−1).
Peptide‐Based Supramolecular Therapeutics for Fighting Major Diseases
Authors: Wang Zhongyan , Luo Hongjing , Wang Heping , Xiao Meng , Jia Haixue , Ren Chunhua , Liu Jianfeng
Published: February 2024

Peptide‐based supramolecular therapeutics (PST) refer to those theranostic nanomedicines based on peptide or peptide derivatives self‐assembly that are constructed in vitro or in vivo. Benefiting from the inherent advantages of peptides, such as good biocompatibility, high bioactivity, and flexible tunability, the reported PST have shown excellent application prospects in combating many major diseases including cancer, cardiovascular disease, infectious disease, autoimmune disease, metabolic disease, and so on. Through thoughtful design, the PST can be fabricated in various forms, including self‐assembled precursor molecules, functional nano‐assemblies, and macroscopic large‐scale hydrogels. The involved peptides in the PST can play different roles, such as serving drug carriers for effective delivery, acting as scaffold materials for cell culture, and functioning as bioactive sequences for treating diseases. In this review, a comprehensive overview of traditional strategies is provided to build PST and emphasize their therapeutic applications for fighting major diseases that pose a threat to human life and health. Moreover, the main challenges of PST in systems design, therapeutic application, and clinical translation are also briefly discussed. It is hoped that this review can arouse much more attention to be paid for PST and promote its practical application in the biomedical field.
Nanodiamond Implanted Zinc Metal Anode for Long‐Life Aqueous Zinc Ion Batteries
Authors: Wang Meiling , Zhang Jin , Wu Mengqi , Yang Di , Sun Peiyan , Sun Jie , Zhang Zeyu , Chen Xibang , Ba Junjie , Wang Yizhan , Qiu Jingyi , Wei Yingjin
Published: February 2024

The practical application of aqueous zinc ion batteries is greatly hindered by the severe dendrite growth and side reactions on the Zn metal anode. To address these challenges, nanodiamond (ND) particles are implanted on the Zn foil surface by a straightforward mechanical rolling process, which serves as heterogeneous seeds, enhancing the cycling stability of Zn metal anode. ND particles with carboxyl groups facilitate the even distribution of electric fields and Zn2+ ions in their vicinity, which promotes the homogeneous deposition of Zn. Moreover, the excellent corrosion resistance of ND particles alleviates the side reactions of the electrode, thus effectively protecting the Zn metal anode in aqueous electrolyte. Benefited from these advantages, the ND@Zn anode shows over 4100 h reversible cycles in symmetric cells, and 99.7% Coulombic efficiency in asymmetric cells. The ND@Zn||MnO2 full cell achieves a stable life of 1000 cycles with 87.0% capacity retention at 1 A g−1 current density. This cost‐effective fabrication process holds the potential for scalability, making it amenable to large‐scale production of zinc metal anodes.
Ordered Phase Distribution of Quasi‐2D Perovskites Controlled by a Supramolecular Approach Enables Efficient Blue Light‐Emitting Diodes
Authors: Yuan Shichen , Fang Tao , Han Boning , Shan Qingsong , Wei Changting , Zheng Xin , Li Xiansheng , Xu Bo , Zeng Haibo
Published: February 2024

Quasi‐2D perovskites demonstrate exceptional luminescent properties, mainly attributed to heightened radiative recombination facilitated by the energy transfer process among spontaneous quantum‐well structures featuring varied n‐value distributions. However, the rapid crystallization process often induces uncontrolled variations in phase composition, characterized by distinct “n” values, leading to suboptimal energy transfer efficiency. In this study, an innovative supramolecular strategy utilizing cryptand is introduced as an additive to regulate the phase distribution within quasi‐2D perovskite films. Cryptand effectively inhibited the aggregation of PEA+ and the formation of unsaturated Pb‐X coordination compounds, thereby suppressing the generation of low‐“n” phases. This intervention resulted in a continuous series of ordered intermediate phases with higher “n” values. The graded electronic structure facilitated efficient energy transfer from low‐“n” to high‐“n” phases, promoting effective radiation recombination. As a result, the optimized PeLEDs emitting at 490 nm demonstrated a remarkable external quantum efficiency (EQE) enhancement to 10.16%, compared to the reference device with an EQE of 2.33%. The device also exhibited impressive spectral and operational stability. The findings establish a viable strategy for precise phase distribution regulation in quasi‐2D perovskites, offering great potential for high‐performance blue PeLEDs.
Patterned Chiral Perovskite Film for Self‐Driven Stokes Photodetectors
Authors: Wang Chao , Li Guoyi , Dai Zhipeng , Tian Wei , Li Liang
Published: February 2024

Polarization detection plays an essential role in a wide range of fields, including target identification, 3D reconstruction, and robotic vision. Self‐driven on‐chip full‐Stokes photodetectors are urgently required to meet the trend of miniaturization and integration. Nevertheless, how to fulfill efficient circular and linear polarimetry simultaneously with sufficient recognition effectiveness in a compact device is a great challenge. Herein, a patterned chiral perovskite film is fabricated by imprinting strategy, and vertically‐structured self‐driven Stokes photodetector is demonstrated, which can recognize various polarization states at 0 V. Through patterned design of the chiral perovskite film by integrating circle and nanowire structure, flexible tuning of circular and linear polarization components within the detector is achieved, enabling the detector to strike a balance between circular and linear polarization detection ability when recognizing arbitrary polarization light. The maximum circular polarization sensitivity factor and linear polarization ratio can reach 0.125 and 1.5, respectively. By optimizing well‐defined patterned shape, the resultant detector can recognize polarized light with an average recognition error <7%. This work opens an avenue toward the fabrication of self‐driven filterless Stokes detectors based on patterned chiral perovskite film for accurate detection of arbitrary polarization states.
Fenton‐like Reaction Inspired “·OH Catalyzed” Osteogenic Process for the Treatment of Osteoporosis
Authors: Wang Jingcheng , Ye Jing , Yang Guoyu , Xie Jialiang , Miao Xinxin , Deng Jianjian , Wu Tianlong , Cheng Xigao , Wang Xiaolei
Published: February 2024

Inspired by the Fenton‐like reaction, this work combines copper peroxide (CP) nanoparticles with black phosphorus (BP) nanosheets to form a hydroxyl radical (·OH)‐centered “catalytic” osteogenic system. CP‐produced ·OH interacts with BP to rapidly produce a large amount of phosphate ions, thus accelerating self‐mineralization and promoting bone formation. In turn, BP not only exerts anti‐inflammatory effects, thereby providing a favorable microenvironment for bone formation, but also offsets the potential toxicity of CP induced by reactive oxygen species (ROS). Together with copper ions (Cu2+), phosphate ions are also released as a byproduct of this process, which can contribute to the comprehensive promotion of osteogenesis.
Cryo‐Electron Microscopy Reveals Na Infiltration into Separator Pore Free‐Volume as a Degradation Mechanism in Na Anode:Liquid Electrolyte Electrochemical Cells
Authors: Matthews Kevin C. , Rush Braxton , Gearba Raluca , Guo Xuelin , Yu Guihua , Warner Jamie H.
Published: February 2024

Batteries utilizing a sodium (Na) metal anode with a liquid electrolyte are promising for affordable large‐scale energy storage. However, a deep understanding of the intrinsic degradation mechanisms is limited by challenges in accessing the buried interfaces. Here, cryogenic electron microscopy of intact electrode:separator:electrode stacks is performed and degradation and failure of symmetric Na||Na coin cells occurs through the infiltration of Na metal through the pores of the separator rather than by mechanical puncturing by dendrites is revealed. It is shown the interior structure of the cell (electrode:separator:electrode) must be preserved and deconstructing the cell into different layers for characterization results in artifacts. In intact cell stacks, minimal liquid is found between the electrodes and separator, leading to intimate electrode:separator interfaces. After electrochemical cycling, Na infiltrates into the pore free‐volume, growing through the separator to create electrical shorts and degradation. The Na infiltration occurs at interfacial regions devoid of solid‐electrolyte interphase (SEI), revealing SEI plays an important role in preventing Na from growing into the separator by being a physical barrier that the plated Na cannot penetrate. These results shed new light on the fundamental failure mechanisms in Na batteries and demonstrate the importance of preserving the cell structure and buried interfaces.
Self‐Powered Photodetector Based on Perovskite/Ge Heterojunction with High Responsivity
Authors: Wang Zeshu , Geng Xiangshun , Jin Jialun , Zhang Peigen , Zhang Li , Li Yuanyuan , Du Jingbo , He Yichu , Zhang Minshu , Peng Jiali , Qin Ken , Dun Guanhua , Wang Chunlin , Tian He , Xie Dan , Yang Yi , Ren Tian‐Ling
Published: February 2024

Self‐powered photodetectors (SPDs) are regarded as a new type of photodetectors without external energy sources, exhibiting great potential in the next generation of image sensing, biological detection, and robotics. Here, single crystal CH(NH2)2PbBr3 (FAPbBr3) perovskite with a low trap density of 1.64 × 109 cm−3 is directly integrated onto single crystal germanium (Ge). The band structure of the heterojunction belongs to type‐II alignment type, which is beneficial to the achievement of high responsivity. Therefore, the fabricated Au/FAPbBr3/Ge/Au detector exhibits a high responsivity of 0.33 A W−1, detectivity up to 3.83 × 1011 Jones and relatively fast decay time of 4.94 ms without external bias under 520 nm laser illumination. In addition, a prototype of an imaging system is set up utilizing the photodetector as a sensing pixel, from which the imaging function is verified. This work demonstrates a facile strategy for designing high‐performance SPDs.
3D‐Printed Lipid Mesophases for the Treatment of Chronic Liver Disease
Authors: Carone Marianna , Gazzi Rafaela , Eugster Remo , Gelli Rita , Manten Niklaas , Ganguin Aymar A. , Valerio Silvia Di , Yadav Garima , Castaldo Pasqualina , Mezzenga Raffaele , Luciani Paola , Aleandri Simone
Published: February 2024

Although lipid‐based formulations are an attractive approach for enhancing the oral bioavailability of lipophilic drugs, their addition into solid oral dosage forms has been proven challenging due to their high viscosity and heat sensitivity. Therefore, unlike the traditional tableting process, this study employed semi‐solid extrusion 3D‐printing to produce–at room temperature–gastro‐resistant printlets containing a high percentage of bioactive lipids for the effective delivery of lipophilic drugs through self‐emulsification. The bio‐compatible lipidic mesophase ink, owing to a tunable 3D nanostructure, is employed as a starting material to produce printlets via additive manufacturing. An active lipid mixture – with antifibrotic properties – is blended with the antioxidant vitamin E and water, and the ink printability is optimized by carefully tailoring its composition, and thus its phase identity. The obtained printlets disintegrated upon contact with intestinal fluids forming colloidal structures that enhanced the solubility of a poorly water‐soluble drug. The printlets exhibited antifibrotic activity on human hepatic stellate cells, LX‐2, suggesting that the generated self‐emulsified colloidal structures made both the fibrosis‐resolving bioactive excipients and the drug promptly available, enhancing their cell uptake and, in turn, their therapeutic activity.
Considerations for the Design and Rapid Manufacturing of Pop‐Up MEMS Devices
Authors: Ramirez Serrano Francisco , Steinhardt Emma , Wood Robert J.
Published: February 2024

The rising number of devices created using pop‐up microelectromechanical systems (MEMS) and related folding‐based assembly techniques highlights the need for robust design and manufacturing workflows to support the wide range of device variations. To push the bounds of miniaturization, design for manufacturing is key in dealing with fabrication challenges. Iterative building of intermediate device prototypes is a promising way to explore an often very large design space and can highlight mechanical limitations that may not be obvious to the designer. Manufacturing of pop‐up MEMS devices is, however, typically a lengthy process with lamination taking a significant percentage of the build time, compared to layer machining and component assembly. To expedite the design process, researchers often prototype multiple iterations at larger scales prior to committing to at‐scale designs. In this study, an at‐scale rapid prototyping workflow for pop‐up MEMS devices is introduced. This study also includes flexure design considerations for castellated hinges, to approach the behavior of an ideal pin joint. The new proposed workflow uses more accessible lower‐cost equipment and materials and reduces lamination time by over 95% (10 min lamination vs a 3.5 h lamination) compared to the previous heated press process, which is validated through a series of prototypes.
Heterostructure of Reduced Titanium Dioxide Nanorods and Small Molecules Leads to Photo‐Induced Negative Differential Resistance Behaviors
Authors: Lee Gyeongho , Han Youngmin , Lee Ho kyung , Yoo Hocheon , Kim Yeong Jae
Published: February 2024

Negative differential resistance (NDR) is of considerable interest due to the uncommon characteristic of having a region where the current decreases as the applied voltage bias increases. However, it is difficult to reproduce NDR devices and evaluate their reliability and stability because of the unstable NDR behaviors. In this paper, a highly stable photo‐induced hybrid photonic (HP)‐NDR device is presented for practical applications, which has heterostructure between TiO2‐x nanorods formed by oblique angle deposition and dinaphtho[2,3‐b:2′,3′‐f]‐thieno[3,2‐b]thiophene. The mechanism of NDR behaviors is investigated through morphological analysis, energy band structure, and electrical characteristics. In addition, diverse bias stress and endurance measurements are performed to demonstrate the reliability of the HP‐NDR device. As a result, the NDR behavior lasts up to 1,000 s in each bias stress and 38,850 cycles in the repeated current–voltage (I–V) characteristics Thus, the study has successfully achieved robust HP‐NDR devices with potential for practical applications.
Piezoelectric Multi‐Channel Bilayer Transducer for Sensing and Filtering Ossicular Vibration
Authors: Yüksel Muhammed Berat , Atik Ali Can , Külah Haluk
Published: February 2024

This paper presents an acoustic transducer for fully implantable cochlear implants (FICIs), which can be implanted on the hearing chain to detect and filter the ambient sound in eight frequency bands between 250 and 6000 Hz. The transducer dimensions are conventional surgery compatible. The structure is formed with 3  × 3 × 0.36 mm active space for each layer and 5.2 mg total active mass excluding packaging. Characterization of the transducer is carried on an artificial membrane whose vibration characteristic is similar to the umbo vibration. On the artificial membrane, piezoelectric transducer generates up to 320.3 mVppunder 100 dB sound pressure level (SPL) excitation and covers the audible acoustic frequency. The measured signal‐to‐noise‐ratio (SNR) of the channels is up to 84.2 dB. Sound quality of the transducer for fully implantable cochlear implant application is graded with an objective qualification method (PESQ) for the first time in the literature to the best of the knowledge, and scored 3.42/4.5.
A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2‐Positive Breast Cancer
Authors: Zhao Li , Chang Fei , Tong Yao , Yin Jiawei , Xu Jiawen , Li Hui , Du Lutao , Jiang Yanyan
Published: February 2024

Anti‐HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2‐positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold‐silver hollow nanoshells (AuAg HNSs) with exceptional near‐infrared (NIR) absorption capability, the small‐molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo‐and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT‐modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF‐κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.
DNMT3A Cooperates with YAP/TAZ to Drive Gallbladder Cancer Metastasis
Authors: Xu Sunwang , Yuan Zhiqing , Jiang Cen , Chen Wei , Li Qiwei , Chen Tao
Published: February 2024

Gallbladder cancer (GBC) is an extremely lethal malignancy with aggressive behaviors, including liver or distant metastasis; however, the underlying mechanisms driving the metastasis of GBC remain poorly understood. In this study, it is found that DNA methyltransferase DNMT3A is highly expressed in GBC tumor tissues compared to matched adjacent normal tissues. Clinicopathological analysis shows that DNMT3A is positively correlated with liver metastasis and poor overall survival outcomes in patients with GBC. Functional analysis confirms that DNMT3A promotes the metastasis of GBC cells in a manner dependent on its DNA methyltransferase activity. Mechanistically, DNMT3A interacts with and is recruited by YAP/TAZ to recognize and access the CpG island within the CDH1 promoter and generates hypermethylation of the CDH1 promoter, which leads to transcriptional silencing of CDH1 and accelerated epithelial‐to‐mesenchymal transition. Using tissue microarrays, the association between the expression of DNMT3A, YAP/TAZ, and CDH1 is confirmed, which affects the metastatic ability of GBC. These results reveal a novel mechanism through which DNMT3A recruitment by YAP/TAZ guides DNA methylation to drive GBC metastasis and provide insights into the treatment of GBC metastasis by targeting the functional connection between DNMT3A and YAP/TAZ.