bluuebunny/crossref_metadata_2025 huggingface dataset:
Egg incubation position affects toxicity of air cell administered polychlorinated biphenyl 126 (3,3′,4,4′,5-pentachlorobiphenyl) in chicken (Gallus gallus) embryos
Authors: McKernan Moira A. , Rattner Barnett A. , Hale Robert C. , Ottinger Mary Ann
Published: November 2007

The avian egg is used extensively for chemical screening and determining the relative sensitivity of species to environmental contaminants (e.g., metals, pesticides, polyhalogenated compounds). The effect of egg incubation position on embryonic survival, pipping, and hatching success was examined following air cell administration of polychlorinated biphenyl (PCB) congener 126 (3,3′,4,4′,5-pentachlorobiphenyl [PCB 126]; 500–2,000 pg/g egg) on day 4 of development in fertile chicken (Gallus gallus) eggs. Depending on dose, toxicity was found to be up to nine times greater in vertically versus horizontally incubated eggs. This may be due to enhanced embryonic exposure to the injection bolus in vertically incubated eggs compared to more gradual uptake in horizontally incubated eggs. Following air cell administration of PCB 126, horizontal incubation of eggs may more closely approximate uptake and toxicity that has been observed with naturally incorporated contaminants. These data have implications for chemical screening and use of laboratory data for ecological risk assessments.
Lead toxicity in alfalfa plants exposed to phytohormones and ethylenediaminetetraacetic acid monitored by peroxidase, catalase, and amylase activities
Authors: López Martha L. , Peralta-Videa Jose R. , Castillo-Michel Hiram , Martinez-Martinez Alejandro , Duarte-Gardea Maria , Gardea-Torresdey Jorge L.
Published: November 2007

This manuscript describes the toxicity of lead in alfalfa plants treated with ethylenediaminetetraacetic acid (EDTA) and the phytohormones indole-3-acetic-acid (IAA), gibberellic acid (GA), and kinetin (KN), on catalase (CAT), ascorbate peroxidase (APOX), and total amylase activity (TAA). In all cases Pb was used at 40 mg/L; EDTA at 0.2 mM (equimolar to Pb); and IAA, GA, and KN at 1, 10, and 100 μM, respectively. An experiment containing Pb at 40 mg/L, 0.2 mM EDTA, and IAA and KN at 100 μM each was performed to determine changes in TAA. A control (plain nutrient solution) also was used for comparison. In all cases the treatments were performed in triplicate. Standard procedures were followed to determine the activity of the respective enzymes. After 10 d of exposure to the treatments, the leaves were harvested, homogenized, and centrifuged, and the supernatants were analyzed for CAT, APOX, and TAA. All determinations were performed in triplicate. The results demonstrated that CAT was reduced significantly (p < 0.05) by all treatments containing Pb, IAA, and GA at 10 and 100 μM. However, only the treatments Pb/EDTA/KN at 1, 10, and 100 μM reduced the APOX. The TAA in leaves of alfalfa plants was increased significantly (p < 0.05) by all treatments. Overall, the results suggest that the CAT tests showed no lead toxicity to the alfalfa seedlings. However IAA at 10 and 100 μM revealed toxicity to the CAT enzyme. In addition, the APOX tests exhibited no toxicity to the peroxidase enzyme with the exception of Pb/EDTA/KN treatments. Finally, the TAA tests showed high Pb/EDTA/phytohormone toxicity to the amylase enzyme in alfalfa seedlings.
Patient Out-of-Pocket Costs for Biologic Drugs After Biosimilar Competition
Authors: Feng Kimberly , Russo Massimiliano , Maini Luca , Kesselheim Aaron S. , Rome Benjamin N.
Published: March 2024

Importance

Biologic drugs account for a growing share of US pharmaceutical spending. Competition from follow-on biosimilar products (subsequent versions that have no clinically meaningful differences from the original biologic) has led to modest reductions in US health care spending, but these savings may not translate to lower out-of-pocket (OOP) costs for patients.

Objective

To investigate whether biosimilar competition is associated with lower OOP spending for patients using biologics.

Design, Setting, and Participants

This cohort study used a national commercial claims database (Optum Clinformatics Data Mart) to identify outpatient claims for 1 of 7 clinician-administered biologics (filgrastim, infliximab, pegfilgrastim, epoetin alfa, bevacizumab, rituximab, and trastuzumab) from January 2009 through March 2022. Claims by commercially insured patients younger than 65 years were included.

Exposure

Year relative to first biosimilar availability and use of original or biosimilar version.

Main Outcomes and Measures

Patients’ annual OOP spending on biologics for each calendar year was determined, and OOP spending per claim between reference biologic and biosimilar versions was compared. Two-part regression models assessed for differences in OOP spending, adjusting for patient and clinical characteristics (age, sex, US Census region, health plan type, diagnosis, and place of service) and year relative to initial biosimilar entry.

Results

Over 1.7 million claims from 190 364 individuals (median [IQR] age, 53 [42-59] years; 58.3% females) who used at least 1 of the 7 biologics between 2009 and 2022 were included in the analysis. Over 251 566 patient-years of observation, annual OOP costs increased before and after biosimilar availability. Two years after the start of biosimilar competition, the adjusted odds ratio of nonzero annual OOP spending was 1.08 (95% CI, 1.04-1.12; P < .001) and average nonzero annual spending was 12% higher (95% CI, 10%-14%; P < .001) compared with the year before biosimilar competition. After biosimilars became available, claims for biosimilars were more likely than reference biologics to have nonzero OOP costs (adjusted odds ratio, 1.13 [95% CI, 1.11-1.16]; P < .001) but had 8% lower mean nonzero OOP costs (adjusted mean ratio, 0.92 [95% CI, 0.90-0.93; P < .001). Findings varied by drug.

Conclusions and Relevance

Findings of this cohort study suggest that biosimilar competition was not consistently associated with lower OOP costs for commercially insured outpatients, highlighting the need for targeted policy interventions to ensure that the savings generated from biosimilar competition translate into increased affordability for patients who need biologics.
The Subjective Interpretation of the Medical Evidence
Authors: Bauchner Howard , Ioannidis John P. A.
Published: March 2024

This Viewpoint discusses whether commonly occuring, sometimes divergent interpretations of new evidence’s validity and usefulness should be explained when experts and guideline committees provide recommendations for screening or treatment.
Prevalence of Medical Payment Products Promoted on US Hospitals’ Websites
Authors: Randall Samantha , Wong Nicholas , Rohrer Josephine , Nguyen Nina Linh , Trish Erin , Duffy Erin L.
Published: March 2024

This cross-sectional study examines the prevalence of hospital-promoted medical payment products (MPPs) by whether hospitals offered any MPP or an interest-bearing MPP.
Outcomes After Initiation of Medications for Alcohol Use Disorder at Hospital Discharge
Authors: Bernstein Eden Y. , Baggett Travis P. , Trivedi Shrunjal , Herzig Shoshana J. , Anderson Timothy S.
Published: March 2024

Importance

US Food and Drug Administration–approved medications for alcohol use disorder (MAUD) are significantly underused. Hospitalizations may provide an unmet opportunity to initiate MAUD, but few studies have examined clinical outcomes of patients who initiate these medications at hospital discharge.

Objective

To investigate the association between discharge MAUD initiation and 30-day posthospitalization outcomes.

Design, Setting, and Participants

This cohort study was conducted among patients with Medicare Part D who had alcohol-related hospitalizations in 2016. Data were analyzed from October 2022 to December 2023.

Exposures

Discharge MAUD initiation was defined as oral naltrexone, acamprosate, or disulfiram pharmacy fills within 2 days of discharge.

Main outcomes

The primary outcome was a composite of all-cause mortality or return to hospital (emergency department visits and hospital readmissions) within 30 days of discharge. Secondary outcomes included these components separately, return to hospital for alcohol-related diagnoses, and primary care or mental health follow-up within 30 days of discharge. Propensity score 3:1 matching and modified Poisson regressions were used to compare outcomes between patients who received and did not receive discharge MAUD.

Results

There were 6794 unique individuals representing 9834 alcohol-related hospitalizations (median [IQR] age, 54 [46-62] years; 3205 hospitalizations among females [32.6%]; 1754 hospitalizations among Black [17.8%], 712 hospitalizations among Hispanic [7.2%], and 7060 hospitalizations among White [71.8%] patients). Of these, 192 hospitalizations (2.0%) involved discharge MAUD initiation. After propensity matching, discharge MAUD initiation was associated with a 42% decreased incidence of the primary outcome (incident rate ratio, 0.58 [95% CI, 0.45 to 0.76]; absolute risk difference, −0.18 [95% CI, −0.26 to −0.11]). These findings were consistent among secondary outcomes (eg, incident rate ratio for all-cause return to hospital, 0.56 [95% CI, 0.43 to 0.73]) except for mortality, which was rare in both groups (incident rate ratio, 3.00 [95% CI, 0.42 to 21.22]). Discharge MAUD initiation was associated with a 51% decreased incidence of alcohol-related return to hospital (incident rate ratio, 0.49 [95% CI, 0.34 to 0.71]; absolute risk difference, −0.15 [95% CI, −0.22 to −0.09]).

Conclusion and relevance

In this cohort study, discharge initiation of MAUD after alcohol-related hospitalization was associated with a large absolute reduction in return to hospital within 30 days. These findings support efforts to increase uptake of MAUD initiation at hospital discharge.
Multi‐scale nested UNet with transformer for colorectal polyp segmentation
Authors: Wang Zenan , Liu Zhen , Yu Jianfeng , Gao Yingxin , Liu Ming
Published: March 2024

Background

Polyp detection and localization are essential tasks for colonoscopy. U‐shape network based convolutional neural networks have achieved remarkable segmentation performance for biomedical images, but lack of long‐range dependencies modeling limits their receptive fields.

Purpose

Our goal was to develop and test a novel architecture for polyp segmentation, which takes advantage of learning local information with long‐range dependencies modeling.

Methods

A novel architecture combining with multi‐scale nested UNet structure integrated transformer for polyp segmentation was developed. The proposed network takes advantage of both CNN and transformer to extract distinct feature information. The transformer layer is embedded between the encoder and decoder of a U‐shape net to learn explicit global context and long‐range semantic information. To address the challenging of variant polyp sizes, a MSFF unit was proposed to fuse features with multiple resolution.

Results

Four public datasets and one in‐house dataset were used to train and test the model performance. Ablation study was also conducted to verify each component of the model. For dataset Kvasir‐SEG and CVC‐ClinicDB, the proposed model achieved mean dice score of 0.942 and 0.950 respectively, which were more accurate than the other methods. To show the generalization of different methods, we processed two cross dataset validations, the proposed model achieved the highest mean dice score. The results demonstrate that the proposed network has powerful learning and generalization capability, significantly improving segmentation accuracy and outperforming state‐of‐the‐art methods.

Conclusions

The proposed model produced more accurate polyp segmentation than current methods on four different public and one in‐house datasets. Its capability of polyps segmentation in different sizes shows the potential clinical application
Bioprinting of Perfusable Vascularized Organ Models for Drug Development via Sacrificial‐Free Direct Ink Writing
Authors: Wu Dongwei , Pang Shumin , Berg Johanna , Mei Yikun , Ali Ahmed S. M. , Röhrs Viola , Tolksdorf Beatrice , Hagenbuchner Judith , Ausserlechner Michael J. , Deubzer Hedwig E. , Gurlo Aleksander , Kurreck Jens
Published: March 2024

3D bioprinting enables the fabrication of human organ models that can be used for various fields of biomedical research, including oncology and infection biology. An important challenge, however, remains the generation of vascularized, perfusable 3D models that closely simulate natural physiology. Here, a novel direct ink writing (DIW) approach is described that can produce vascularized organ models without using sacrificial materials during fabrication. The high resolution of the method allows the one‐step generation of various sophisticated hollow geometries. This sacrificial‐free DIW (SF‐DIW) approach is used to fabricate hepatic metastasis models of various cancer types and different formats for investigating the cytostatic activity of anti‐cancer drugs. To this end, the models are incorporated into a newly developed perfusion system with integrated micropumps and an agar casting step that improves the physiological features of the bioprinted tissues. It is shown that the hepatic environment of the tumor models is capable of activating a prodrug, which inhibits breast cancer growth. This versatile SF‐DIW approach is able to fabricate complicated perfusable constructs or microfluidic chips in a straightforward and cost‐efficient manner. It can also be easily adapted to other cell types for generating vascularized organ tissues or cancer models that may support the development of new therapeutics.
Photosensitive Nanoprobes for Rapid High Purity Isolation and Size‐Specific Enrichment of Synthetic and Extracellular Vesicle Subpopulations
Authors: Weerakkody Jonathan S. , Tseng Tiffany , Topper Mackenzie , Thoduvayil Sikha , Radhakrishnan Abhijith , Pincet Frederic , Kyriakides Themis R. , Gunasekara Roshan W. , Ramakrishnan Sathish
Published: March 2024

The biggest challenge in current isolation methods for lipid bilayer‐encapsulated vesicles, such as exosomes, secretory, and synthetic vesicles, lies in the absence of a unified approach that seamlessly delivers high purity, yield, and scalability for large‐scale applications. To address this gap, an innovative method is developed that utilizes photosensitive lipid nanoprobes for the efficient isolation of vesicles and sorting them into subpopulations based on size. The photosensitive component in the probe undergoes cleavage upon exposure to light, facilitating the release of vesicles in their near‐native form. The method demonstrates a superior ability in isolating high purity extracellular vesicles from complex biological media and separating them into size‐based subpopulations within 1 h, achieving more efficiency and purity than ultracentrifugation. Furthermore, this method's cost‐effectiveness and rapid enrichment of the vesicles align with demands for large‐scale isolation and downstream analyses of nucleic acids and proteins. The method opens new avenues in exploring, analyzing, and utilizing synthetic and extracellular vesicle subpopulations in various biomedical applications, including diagnostics, therapeutic delivery, and biomarker discovery.
Engineering Spin State in Spinel Co3O4 nanosheets by V‐Doping for Bidirectional Catalysis of Polysulfides in Lithium–Sulfur Batteries
Authors: Zhou Wei , Chen Minzhe , Zhao Dengke , Zhu Chuheng , Wang Nan , Lei Wen , Guo Yan , Li Ligui
Published: March 2024

The slow bidirectional conversion and fast shuttling of lithium polysulfides (LiPSs) remain the main obstacles that inhibit the practical application of lithium sulfur batteries (LSBs). Here, by engineering the in‐spin state of spinel oxides, V doping‐induced hexagonal nanosheets (V‐Co3O4 NS) with intermediate spin state (IS, t2g5 eg1) can form stable bond order toward LiS* based on the ligand field theory and molecular orbital theory, thus effectively accelerating the sulfur conversion kinetics. Owing to these merits, the V‐Co3O4 NS modified separator base battery achieves a high areal capacity of 15.37 mAh cm−2 with sulfur loading of 15.4 mg cm−2, and it displays a low‐capacity attenuation of 0.015% each cycle at 3.0 C for 1900 cycles.
Free‐Standing Bacterial Cellulose‐Templated Radiative Cooling Liquid Crystal Films with Self‐Adaptive Solar Transmittance Modulation
Authors: Li Binxuan , Valenzuela Cristian , Liu Yuan , Zhang Xuan , Yang Yanzhao , Chen Yuanhao , Wang Ling , Feng Wei
Published: March 2024

Passive radiative cooling materials can efficiently reflect solar radiation and spontaneously dissipate heat through the long‐wave infrared (LWIR) transmission window to the coldouter space. They are highly attractive for application in walls and roofs of sustainable energy‐efficient buildings, but it is a challenging task to develop switchable radiative coolers for transparent windows. Herein, free‐standing bacterial cellulose‐templated radiative cooling liquid crystal films with high LWIR emissivity and self‐adaptive solar transmittance are reported. Biosynthetic silanized bacterial cellulose with 3D interconnected porous nanostructure is harnessed as a robust template for confining novel liquid crystals with smectic A to chiral nematic phase transition, thereby endowing the film with high solar transmittance modulation ability. The resulting film is found to not only exhibit a remarkable LWIR emissivity, but also adaptively change its solar transmittance between a transparent state and an opaque state according to environmental temperature variation. Outdoor radiative cooling experiments are performed, and the energy‐saving performance is evaluated through a simulation of a 12‐story reference office building with the films applied as radiative cooling windows. This research can shine light on the development of advanced radiative cooling materials with switchable transmittance and their widespread applications in buildings, vehicles, and transparent photovoltaics.
Ultralong MRTADF and Room‐Temperature Phosphorescence Enabled Color‐Tunable and High‐Temperature Dual‐Mode Organic Afterglow from Indolo[3,2‐b]carbazole
Authors: Xu Lihua , Wei Hengshan , Xie Guohua , Xu Bingjia , Zhao Jiang
Published: March 2024

Organic afterglow can be generated from persistent thermally activated delayed fluorescence (pTADF) or organic ultralong room temperature phosphorescence (OURTP), but the pTADF plus OURTP type organic afterglow is challenging to achieve, especially for the color‐tunable and high‐temperature ones. Herein, an accessible strategy toward such dual‐mode afterglow is presented by doping the indolo[3,2‐b]carbazole (ICZ‐p1) into polymethyl methacrylate (PMMA). The resulting films exhibit photo‐activated afterglow with two persistent emission peaks of ca. 435 and 497 nm. Impressively, their longest lifetimes respectively reach to 2.28 and 2.47 s at 298 K, along with 0.32 and 0.42 s at 360 K, enabling the afterglow at room and high temperature. Experimental and theoretical results reveal that the photo‐activated afterglow is associated with the elimination of molecular O2 inside film and composed by the pTADF with multi‐resonance (MR) effect and OURTP. By altering the temperature from 77 to 358 K, the color‐tunable afterglows of green and blue are harvested at such temperature ranges. Benefiting from the multi‐resonance thermally activated delayed fluorescence (MRTADF) characteristics, this emitter can release narrow‐band electroluminescence. Consequently, the results obtained here may offer important references for chasing MRTADF plus OURTP‐type dual‐mode organic afterglow showing color‐tunable and high‐temperature features.
Synthesis on NIR‐II Multifunctional Imaging and Photothermal Therapy of a Novel Water‐Soluble Molecule
Authors: Cao Mengyu , Wang Chang , Wang Fang , Zou Wentao , Yu Bing , Cong Hailin , Shen Youqing
Published: March 2024

The synthesis of water‐soluble symmetric molecules with donor‐acceptor‐donor (D‐A‐D) structure is reported. The compound is connected by π bridge with 2‐bromofluorene external polyethylene glycol 2000 as the shielding unit, and donor component and pyrrolopyrrole (DPP) as the acceptor unit. The D‐A‐D double donor fluorescent molecule P2‐DPP is obtained by coupling reaction. The absorption peak and emission peak of the fluorescent molecule P2‐DPP are 600 and 1020 nm, respectively. It has potential excellent imaging characteristics. It does not need to use nanoparticles formed by the DSPE‐MPEG amphiphilic block to form micelles. The quantum yield reaches 0.6% and the penetration depth can reach 10 mm. The chemical is capable of achieving liver and renal metabolism. It has a good application prospect in the photothermal therapy of mouse tumors and realizes the integration of biological diagnosis and treatment.
Pyroelectric‐Accelerated Perovskite Photodetector for Picosecond Light Detection and Ranging
Authors: Min Liangliang , Sun Haoxuan , Guo Linqi , Zhou Yicheng , Wang Meng , Cao Fengren , Li Liang
Published: March 2024

Light detection and ranging (LiDAR) is indispensable in applications such as unmanned aerial vehicles, autonomous driving, and biomimetic robots. However, the precision and available distance of LiDAR are constrained by the speed and sensitivity of the photodetector, necessitating the use of expensive and energy‐consuming avalanche diodes. To address these challenges, in this study, a pyroelectricity‐based acceleration strategy with 2D‐(graded 3D) perovskite heterojunction is proposed to achieve a record high speed (27.7 ns with an active area of 9 mm2, and 176 ps with an active area of 0.2 mm2) and high responsivity (0.65 A W−1) at zero bias. This success is attributed to the unique mechanism where the electrons from the pyroelectric effect at the Cl‐rich 2D/3D interface directly recombine with excess holes during light–dark transitions, breaking speed limitations related to carrier mobility and capacitive effect. Furthermore, the introduced pyroelectric effect significantly enhances the photoresponse, resulting in a self‐powered external quantum efficiency exceeding 100%. The study also demonstrates precise position detection at the centimeter level. In conclusion, this research presents a pioneering approach for developing high‐speed photodiodes with exceptional sensitivity, mitigating energy and cost concerns in LiDAR applications.
A Viscous‐Biofluid Self‐Pumping Organohydrogel Dressing to Accelerate Diabetic Wound Healing
Authors: Xiao Wuyi , Wan Xizi , Shi Lianxin , Ye Maosheng , Zhang Yikai , Wang Shutao
Published: March 2024

Viscous biofluids on wounds challenge conventional “water‐absorbing” wound dressings in efficient drainage due to their poor fluidity, generally causing prolonged inflammation, anti‐angiogenesis, and delayed wound closure. Herein, it is reported that a self‐pumping organohydrogel dressing (SPD) with aligned hydrated hydrogel channels, prepared by a three‐dimensional‐templated wetting‐enabled‐transfer (3D‐WET) polymerization process, can efficiently drain viscous fluids and accelerate diabetic wound healing. The asymmetric wettability of the hydrophobic–hydrophilic layers and aligned hydrated hydrogel channels enable unidirectional and efficient drainage of viscous fluids away from the wounds, preventing their overhydration and inflammatory stimulation. The organogel layer can adhere onto the skin around the wounds but can be easily detached from the wet wound area, avoiding secondary trauma to the newly formed tissues. Taking a diabetic rat model as an example, the SPD can significantly downregulate the inflammation response by ≈70.8%, enhance the dermal remodeling by ≈14.3%, and shorten wound closure time by about 1/3 compared with the commercial dressing (3M, Tegaderm hydrocolloid thin dressing). This study sheds light on the development of the next generation of functional dressings for chronic wounds involving viscous biofluids.
Bioinspired Bottlebrush Polymers Effectively Alleviate Frictional Damage Both In Vitro and In Vivo
Authors: Pham Duy Anh , Wang Chang‐Sheng , Séguy Line , Zhang Hu , Benbabaali Sabrina , Faivre Jimmy , Sim Sotcheadt , Xie Guojun , Olszewski Mateusz , Rabanel Jean‐Michel , Moldovan Florina , Matyjaszewski Krzysztof , Banquy Xavier
Published: March 2024

Bottlebrush polymers (BB) have emerged as compelling candidates for biosystems to face tribological challenges, including friction and wear. This study provides a comprehensive assessment of an engineered triblock BB polymer's affinity, cell toxicity, lubrication, and wear protection in both in vitro and in vivo settings, focusing on applications for conditions like osteoarthritis and dry eye syndrome. Results show that the designed polymer rapidly adheres to various surfaces (e.g., cartilage, eye, and contact lens), forming a robust, biocompatible layer for surface lubrication and protection. The tribological performance and biocompatibility are further enhanced in the presence of hyaluronic acid (HA) both in vitro and in vivo. The exceptional lubrication performance and favorable interaction with HA position the synthesized triblock polymer as a promising candidate for innovative treatments addressing deficiencies in bio‐lubricant systems.
Direct Laser Writing: From Materials Synthesis and Conversion to Electronic Device Processing
Authors: Pinheiro Tomás , Morais Maria , Silvestre Sara , Carlos Emanuel , Coelho João , Almeida Henrique V. , Barquinha Pedro , Fortunato Elvira , Martins Rodrigo
Published: March 2024

Direct Laser Writing (DLW) has been increasingly selected as a microfabrication route for efficient, cost‐effective, high‐resolution material synthesis and conversion. Concurrently, lasers participate in the patterning and assembly of functional geometries in several fields of application, of which electronics stand out. In this review, recent advances and strategies based on DLW for electronics microfabrication are surveyed and outlined, based on laser material growth strategies. First, the main DLW parameters influencing material synthesis and transformation mechanisms are summarized, aimed at selective, tailored writing of conductive and semiconducting materials. Additive and transformative DLW processing mechanisms are discussed, to open space to explore several categories of materials directly synthesized or transformed for electronics microfabrication. These include metallic conductors, metal oxides, transition metal chalcogenides and carbides, laser‐induced graphene, and their mixtures. By accessing a wide range of material types, DLW‐based electronic applications are explored, including processing components, energy harvesting and storage, sensing, and bioelectronics. The expanded capability of lasers to participate in multiple fabrication steps at different implementation levels, from material engineering to device processing, indicates their future applicability to next‐generation electronics, where more accessible, green microfabrication approaches integrate lasers as comprehensive tools.
An Antibody‐CRISPR/Cas Conjugate Platform for Target‐Specific Delivery and Gene Editing in Cancer
Authors: Yang Seungju , Im San Hae , Chung Ju Yeon , Lee Juhee , Lee Kyung‐Hun , Kang Yoo Kyung , Chung Hyun Jung
Published: March 2024

The CRISPR/Cas system has been introduced as an innovative tool for therapy, however achieving specific delivery to the target has been a major challenge. Here, an antibody‐CRISPR/Cas conjugate platform that enables specific delivery and target gene editing in HER2‐positive cancer is introduced. The CRISPR/Cas system by replacing specific residues of Cas9 with an unnatural amino acid is engineered, that can be complexed with a nanocarrier and bioorthogonally functionalized with a monoclonal antibody targeting HER2. The resultant antibody‐conjugated CRISPR/Cas nanocomplexes can be specifically delivered and induce gene editing in HER2‐positive cancer cells in vitro. It is demonstrated that the in vivo delivery of the antibody‐CRISPR/Cas nanocomplexes can effectively disrupt the plk1 gene in HER2‐positive ovarian cancer, resulting in substantial suppression of tumor growth. The current study presents a useful therapeutic platform for antibody‐mediated delivery of CRISPR/Cas for the treatment of various cancers and genetic diseases.
Ni‐Single Atoms Modification Enabled Kinetics Enhanced and Ultra‐Stable Hard Carbon Anode for Sodium‐Ion Batteries
Authors: Qiu Daping , Zhao Wanting , Zhang Biao , Ahsan Muhammad Tayyab , Wang Yuehui , Zhang Lulu , Yang Xuelin , Hou Yanglong
Published: March 2024

Hard carbon with randomly oriented interlayers is the most promising candidate for the anode of commercial sodium‐ion batteries (SIBs). Nevertheless, its sluggish sodium storage kinetics and unsatisfactory cycling stability are bottlenecks to its implementation. Herein, a metal‐single atom modification strategy is proposed to construct a Ni‐single atoms modified N, P co‐doped hard carbon (Ni‐NPC) with a Ni content of ≈5.65 wt%. As an anode for SIBs, Ni‐NPC exhibits far superior initial Coulombic efficiency, reversible specific capacity, rate capability, and cycling stability to N, P co‐doped hard carbon. Combining in situ EIS and ex‐situ XPS,this study reveals that Ni‐single atoms modulate the composition of the solid electrolyte interface layer, thereby improving the cycling stability of Ni‐NPC. Theoretical calculation and kinetics analysis suggest that Ni‐single atoms are the promoters of the diffusion of Na+. Furthermore, with the aid of systematic in situ characterizations, the structural evolution of Ni‐NPC at different sodium storage stages is identified. This work proposes a potential strategy for simultaneously improving the sodium storage kinetics and cycling stability of hard carbon anodes, and elucidates the improvement mechanism of this strategy.
A study of the spatial distribution characteristics of Chinese surnames
Authors: Fan Xiaohui , Gao Yuan , Liu Yan , Li Xiaomeng , Yuan Yida , Chen Liujun , Chen Jiawei
Published: March 2024

Objectives

The spatial distribution of Chinese surnames is diverse and provides rich information about the evolution of human society. This study aims to propose several indices to quantify the spatial distribution characteristics of Chinese common surnames and to explore how these distributions are related to historical evolution.

Methods

This study uses data from China's ID information system covering 1.28 billion people across 362 cities. Based on the location quotient, several new concepts, such as “moderately concentrated cities” and “highly concentrated cities,” are defined. Then indices such as range, ununiformity and spatial autocorrelation are proposed and calculated to analyze the spatial characteristics of Chinese common surnames.

Results

A significant correlation is observed between the commonness of a surname and its spatial characteristics: the more common the surname, the wider its spatial range, the lower the ununiformity, and the higher the autocorrelation coefficient. These patterns reflect the complex interplay of historical, geographical, and cultural factors influencing surname spatial distribution.

Conclusions

The spatial distribution of Chinese surnames is intricately linked to their historical evolution. Most common surnames, often with deeper historical roots, exhibit wider distributions and lower ununiformity, whereas less common surnames show higher concentrations in specific areas. These quantitative results provide a comprehensive understanding of the evolutionary characteristics of Chinese surnames.
Effect of acidic nano ZSM‐5 modified by hydroxyapatite nanowires on flame‐retardant performance in PLA/IFR composite
Authors: Ma Qin , Lu Jing , Zhai Xiaokun , Teng Hao , Zhang Ruiyan , Luo Faliang
Published: March 2024

Flame‐retardant polylactic acid (PLA) composites play critical role in construction fields. However, it is urgent to develop flame‐retardant PLA composites since PLA inherent flammability and melt dripping. Herein, we utilize intumescent flame retardant (IFR) with hydroxyapatite nanowires/acidic nano ZSM‐5 (HAP/HN) as synergist to improve the PLA flame‐retardant performance. According to scanning electron microscopy (SEM) observation, HN particles were distributed around with HAP and x‐ray diffraction, Fourier transform infrared spectrum show that the HAP/HN particles were successfully developed with the interaction of hydrogen bonds. The flame‐retardant results of PLA composites showed that the limited oxygen index value increased from 18.0% of neat PLA to 38.2% for HAP/HN sample, moreover the peak heat release rate (pHRR) was lower (~65%) than that of neat PLA (553 kW/m2). In addition, the char yield of PLA/IFR/HAP/HN sample increased from 9.5% to 54.2% for PLA/IFR/HN. SEM results showed that the char surface was smoother and denser with incorporation of HAP/HN. TG‐IR test also demonstrated that the intensity of CO was decreased obviously in gas phase due to the addition of HAP.
Rational design of high‐performance epoxy/expandable microsphere foam with outstanding mechanical, thermal, and dielectric properties
Authors: Tang Haiwen , Li Yi , Zhu Ziyi , Zhan Yingqing , Li Ying , Li Kui , Wang Pan , Zhong Fei , Feng Wei , Yang Xulin
Published: March 2024

Previous studies on epoxy foams were subjected to the specific property, and improvements in thermal insulation or dielectric property were usually accompanied by the sacrifice of mechanical strength or thermal stability. The current research reported a high‐performance epoxy foam by the pre‐curing process using E‐51/DDS and expandable microsphere (EMP) as polymer matrix and physical blowing agent, respectively. The effect of EMP loading on the structure & property of epoxy foam was reported. The mean diameter of E‐51/EMP foam was in the range of 19–21 μm. The compression property of E‐51/EMP foam was fit for the power‐law model and its integrity was well maintained during compressive test. Compared with bulky epoxy, a significant decrease of thermal conductivity of 62.93% was observed in 10 wt% EMP‐filled epoxy foam. E‐51/EMP foam showed superior thermal stabilities, with a T5% of over 300°C. The dielectric constant was decreased by 54.5% from 4.92 in bulky epoxy to 2.24 in E‐51/EMP foam (10 wt% EMP). Notably, there was a percolation phenomenon of EMP (6 wt%) regarding on the structure & property of E‐51/EMP foam. This study provides lightweight, robust, high‐temperature‐resistant, and low‐dielectric‐constant epoxy foams with the wide application prospects in buoyant, electronic packaging, and energy‐saving industries.
Development of inducible promoters for regulating gene expression in Clostridium tyrobutyricum for biobutanol production
Authors: Feng Jun , Wang Qingke , Qin Zhen , Guo Xiaolong , Fu Hongxin , Yang Shang‐Tian , Wang Jufang
Published: March 2024

Clostridium tyrobutyricum is an anaerobe known for its ability to produce short‐chain fatty acids, alcohols, and esters. We aimed to develop inducible promoters for fine‐tuning gene expression in C. tyrobutyricum. Synthetic inducible promoters were created by employing an Escherichia coli lac operator to regulate the thiolase promoter (PCathl) from Clostridium acetobutylicum, with the best one (LacI‐Pto4s) showing a 5.86‐fold dynamic range with isopropyl β‐
d‐thiogalactoside (IPTG) induction. A LT‐Pt7 system with a dynamic range of 11.6‐fold was then created by combining LacI‐Pto4s with a T7 expression system composing of RNA polymerase (T7RNAP) and Pt7lac promoter. Furthermore, two inducible expression systems BgaR‐PbgaLA and BgaR‐PbgaLB with a dynamic range of ~40‐fold were developed by optimizing a lactose‐inducible expression system from Clostridium perfringens with modified 5′ untranslated region (5′ UTR) and ribosome‐binding site (RBS). BgaR‐PbgaLB was then used to regulate the expressions of a bifunctional aldehyde/alcohol dehydrogenase encoded by adhE2 and butyryl‐CoA/acetate Co‐A transferase encoded by cat1 in C. tyrobutyricum wild type and Δcat1::adhE2, respectively, demonstrating its efficient inducible gene regulation. The regulated cat1 expression also confirmed that the Cat1‐catalyzed reaction was responsible for acetate assimilation in C. tyrobutyricum. The inducible promoters offer new tools for tuning gene expression in C. tyrobutyricum for industrial applications.
Inhibition of hyphal formation together with biochar addition promotes erythritol production by Yarrowia lipolytica
Authors: Liu Fangmei , Xia Kai , Chen Yuqing , Zhu Ling , Zhu Lingzhi , Zhao Xuequn , Sha Ruyi , Huang Jun
Published: March 2024

This study aimed to investigate the effect of hyphal formation in Yarrowia lipolytica and biochar addition on erythritol production by submerged fermentation. Hyphal formation significantly inhibited erythritol production by Y. lipolytica. Transcriptome analysis suggested that the impaired erythritol synthesis of hyphal cells was associated with the differential expression of genes involved in amino acid metabolism, lipid metabolism, and cell wall stability. Deletion of RAS2 responsible for yeast‐to‐hypha transition and EYD1 included in erythritol degradation blocked hyphal formation and improved erythritol production. Biochar prepared from corncob, sugarcane bagasse (SB), corn straw, peanut shell, coconut shell, and walnut shell (WS) had a positive effect on erythritol production, of which WS pyrolyzed at 500°C (WSc) performed the best in flask fermentation. In a 3.7 L bioreactor, 220.20 ± 10 g/L erythritol with a productivity of 2.30 ± 0.10 g/L/h was obtained in the presence of 1.4% (w/v) WSc and 0.7% SBc (SB pyrolyzed at 500°C) within 96 h. These results suggest that inhibition of hyphal formation together with biochar addition is an efficient way to promote erythritol production.
Sequence‐based design and construction of synthetic nanobody library
Authors: Liu Chuanyong , Li Yanping , He Qinghua , Fu Jinheng , Wei Qingting , Lin Hao , Luo Ying , Tu Zhui
Published: March 2024

Nanobody (Nb), the smallest antibody fragments known to bind antigens, is now widely applied to various studies, including protein structure analysis, bioassay, diagnosis, and biomedicine. The traditional approach to generating specific nanobodies involves animal immunization which is time‐consuming and expensive. As the understanding of the antibody repertoire accumulation, the synthetic library, which is devoid of animals, has attracted attention widely in recent years. Here, we describe a synthetic phage display library (S‐Library), designed based on the systematic analysis of the next‐generation sequencing (NGS) of nanobody repertoire. The library consists of a single highly conserved scaffold (IGHV3S65*01‐IGHJ4*01) and complementary determining regions of constrained diversity. The S‐Library containing 2.19 × 108 independent clones was constructed by the one‐step assembly and rapid electro‐transformation. The S‐Library was screened against various targets (Nb G8, fusion protein of Nb G8 and green fluorescent protein, bovine serum albumin, ovalbumin, and acetylcholinesterase). In comparison, a naïve library (N‐Library) from the source of 13 healthy animals was constructed and screened against the same targets as the S‐Library. Binders were isolated from both S‐Library and N‐Library. The dynamic affinity was evaluated by the biolayer interferometry. The data confirms that the feature of the Nb repertoire is conducive to reducing the complexity of library design, thus allowing the S‐Library to be built on conventional reagents and primers.
Immunologic tumor microenvironment modulators for turning cold tumors hot
Authors: Khosravi Gholam‐Reza , Mostafavi Samaneh , Bastan Sanaz , Ebrahimi Narges , Gharibvand Roya Safari , Eskandari Nahid
Published: March 2024

Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment (TME). Hot tumors, characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors (ICIs), stand in stark contrast to cold tumors, which lack immune infiltration and remain resistant to therapy. To overcome immune evasion mechanisms employed by tumor cells, novel immunologic modulators have emerged, particularly ICIs targeting cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) and programmed cell death protein 1/programmed death‐ligand 1(PD‐1/PD‐L1). These agents disrupt inhibitory signals and reactivate the immune system, transforming cold tumors into hot ones and promoting effective antitumor responses. However, challenges persist, including primary resistance to immunotherapy, autoimmune side effects, and tumor response heterogeneity. Addressing these challenges requires innovative strategies, deeper mechanistic insights, and a combination of immune interventions to enhance the effectiveness of immunotherapies. In the landscape of cancer medicine, where immune cold tumors represent a formidable hurdle, understanding the TME and harnessing its potential to reprogram the immune response is paramount. This review sheds light on current advancements and future directions in the quest for more effective and safer cancer treatment strategies, offering hope for patients with immune‐resistant tumors.
The effect of a spiritual intelligence‐based counselling programme on suicidal ideation and self‐concept among retirement
Authors: Alshareef Basma Eid , Alfuqaha Othman A.
Published: March 2024

Background

Spiritual counselling techniques can offer individuals a sense of new meaning and a way to cope with difficulties. However, no prior study has specifically examined the effectiveness of a spiritual intelligence counselling programme on suicidal ideation and self‐concept among retired individuals.

Aims

This study aimed to evaluate how a new counselling programme focusing on spiritual intelligence helps retired individuals deal with suicidal ideation and self‐concept.

Materials and Methods

A total of 40 retired individuals were split into two groups: one that received the counselling programme (experimental group = 20) and one that did not (control group = 20) based on their initial scores of suicidal ideation and self‐concept scales. The experimental group went through a 10‐session counselling programme, meeting for 90 min each week from April to June 2023.

Results

Based on means, standard deviations and analysis of variance, results found significant differences in scores between those who underwent the counselling programme and those who did not. The experimental group revealed a decrease in suicidal ideation and an improvement in self‐concept after completing the counselling programme. Males seemed to benefit more from the spiritual intelligence‐based counselling programme than females in reducing suicidal ideation. There was no difference between males and females regarding self‐concept.

Discussion

The spiritual counselling programme improves self‐concept and reduces suicidal ideation among retired individuals.

Conclusion

The results suggest that the spiritual intelligence‐based counselling programme shows promise in addressing mental health issues among retired individuals.
The linear pattern of therapeutic alliance development: Exploring the relationship between alliance trajectories over time and the outcomes of systemic psychotherapy treatment for adaptation disorders
Authors: Prusiński Tomasz
Published: March 2024

Objective

This study aimed to determine the trajectories of therapeutic alliance development in individual systemic psychotherapy for adults with adaptation disorders and the differences in alliance development between groups with different treatment outcomes.

Method

The longitudinal quasi‐experiment included 20 patients undergoing individual outpatient psychotherapy treatment in private practice for over a year. Therapeutic alliance was evaluated three times, by the psychotherapist and the patient simultaneously. Treatment outcomes were estimated twice based on patient ratings. Their clinical significance was assessed using the Reliable Change Index, analysis of variance for independent groups and trend analysis. The analyses concerned global therapeutic alliance and its three dimensions: goals, tasks and bonds.

Results

The study supported the hypothesised linear trend. It also confirmed a greater increase in alliance quality over the course of treatment in patients whose therapy was more successful.

Conclusion

The results indicate that, in patients with adaptation disorders, alliance development in systemic therapy follows a stable linear trend. The linear change observed for global therapeutic alliance is paralleled by similar trends in goals, tasks and bonds. Strong alliance correlates with better treatment outcomes.
Pore structure and oxygen content design of amorphous carbon toward a durable anode for potassium/sodium‐ion batteries
Authors: Shi Xiaodong , Zhou Chuancong , Gao Yuxin , Yang Jinlin , Xie Yu , Feng Suyang , Zhang Jie , Li Jing , Tian Xinlong , Zhang Hui
Published: March 2024

Both sodium‐ion batteries (SIBs) and potassium‐ion batteries (PIBs) are considered as promising candidates in grid‐level energy storage devices. Unfortunately, the larger ionic radii of K+ and Na+ induce poor diffusion kinetics and cycling stability of carbon anode materials. Pore structure regulation is an ideal strategy to promote the diffusion kinetics and cyclic stability of carbon materials by facilitating electrolyte infiltration, increasing the transport channels, and alleviating the volume change. However, traditional pore‐forming agent‐assisted methods considerably increase the difficulty of synthesis and limit practical applications of porous carbon materials. Herein, porous carbon materials (Ca‐PC/Na‐PC/K‐PC) with different pore structures have been prepared with gluconates as the precursors, and the amorphous structure, abundant micropores, and oxygen‐doping active sites endow the Ca‐PC anode with excellent potassium and sodium storage performance. For PIBs, the capacitive contribution ratio of Ca‐PC is 82% at 5.0 mV s−1 due to the introduction of micropores and high oxygen‐doping content, while a high reversible capacity of 121.4 mAh g−1 can be reached at 5 A g−1 after 2000 cycles. For SIBs, stable sodium storage capacity of 101.4 mAh g−1 can be achieved at 2 A g−1 after 8000 cycles with a very low decay rate of 0.65% for per cycle. This work may provide an avenue for the application of porous carbon materials in the energy storage field.
Risks of malignancy in the major nongynecologic cytopathology reporting systems: Critiques and discussions
Authors: Pusztaszeri Marc P. , Saieg Mauro , Baloch Zubair W.
Published: March 2024

The ever‐increasing popularity of standardized systems for reporting cytopathology has led in part to much attention to and importance of the risk stratification schemes, especially the risks of malignancy (ROMs), which are associated with the different diagnostic categories and upon which recommendations for clinical management are based. However, it is well known that the ROM calculations are based on retrospective reviews of the existing literature, representing a heterogeneous patient population, and are plagued by significant biases and variations. Statistically, the ROM represents the post‐test probability of malignancy, which changes with the test result and with the prevalence of malignancy (or pretest probability) in an individual practice setting and individual patient presentation. Therefore, the clinical utility of the ROM is questioned and likely needs a second look in the nongynecologic cytopathology reporting systems. In this communication, the authors discuss the status of the ROM estimates according to the most commonly used nongynecologic reporting systems, including for thyroid, salivary glands, and others, highlighting similarities and differences with a focus on the limitations of ROM estimates and their application in clinical practice.