bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanically activated piezo channels modulate outflow tract valve development through the Yap1 and Klf2-Notch signaling axis
Authors: Duchemin Anne-Laure , Vignes Hélène , Vermot Julien
Published: September 2019

Mechanical forces are well known for modulating heart valve developmental programs. Yet, it is still unclear how genetic programs and mechanosensation interact during heart valve development. Here, we assessed the mechanosensitive pathways involved during zebrafish outflow tract (OFT) valve development in vivo. Our results show that the hippo effector Yap1, Klf2, and the Notch signaling pathway are all essential for OFT valve morphogenesis in response to mechanical forces, albeit active in different cell layers. Furthermore, we show that Piezo and TRP mechanosensitive channels are important factors modulating these pathways. In addition, live reporters reveal that Piezo controls Klf2 and Notch activity in the endothelium and Yap1 localization in the smooth muscle progenitors to coordinate OFT valve morphogenesis. Together, this work identifies a unique morphogenetic program during OFT valve formation and places Piezo as a central modulator of the cell response to forces in this process.
Evolution of neuronal anatomy and circuitry in two highly divergent nematode species
Authors: Hong Ray L , Riebesell Metta , Bumbarger Daniel J , Cook Steven J , Carstensen Heather R , Sarpolaki Tahmineh , Cochella Luisa , Castrejon Jessica , Moreno Eduardo , Sieriebriennikov Bogdan , Hobert Oliver , Sommer Ralf J
Published: September 2019

The nematodes C. elegans and P. pacificus populate diverse habitats and display distinct patterns of behavior. To understand how their nervous systems have diverged, we undertook a detailed examination of the neuroanatomy of the chemosensory system of P. pacificus. Using independent features such as cell body position, axon projections and lipophilic dye uptake, we have assigned homologies between the amphid neurons, their first-layer interneurons, and several internal receptor neurons of P. pacificus and C. elegans. We found that neuronal number and soma position are highly conserved. However, the morphological elaborations of several amphid cilia are different between them, most notably in the absence of ‘winged’ cilia morphology in P. pacificus. We established a synaptic wiring diagram of amphid sensory neurons and amphid interneurons in P. pacificus and found striking patterns of conservation and divergence in connectivity relative to C. elegans, but very little changes in relative neighborhood of neuronal processes. These findings demonstrate the existence of several constraints in patterning the nervous system and suggest that major substrates for evolutionary novelty lie in the alterations of dendritic structures and synaptic connectivity.
We Can Do I.T.: Women in Library Information Technology
Authors: Stayton Jenn
Published: September 2019

A review of the tenth book in Litwin's series on Gender and Sexuality in Information Studies that summarizes the themes of the collection's essays and broadly discusses the impact of editorial choices on the structure and narrative of the work.
Seasonal and inter-annual community structure characteristics of zooplankton driven by water environment factors in a sub-lake of Lake Poyang, China
Authors: Hu Beijuan , Hu Xuren , Nie Xue , Zhang Xiaoke , Wu Naicheng , Hong Yijiang , Qin Hai Ming
Published: September 2019

Background

Sub-lakes are important for the maintenance of the ecosystem integrity of Lake Poyang, and zooplankton play an important role in its substance and energy flow.

Methods

A seasonal investigation of zooplankton was conducted in spring (April), summer (July), autumn (October) and winter (January of the following year) from 2012 to 2016 in a sub-lake of Lake Poyang. The aim of the present study was to understand the seasonal dynamics and interannual variation of zooplankton communities and their relationship to environmental factors.

Results

A total of 115 species were identified in all samples in the four years, which comprised of 87 Rotifera, 13 Cladocera and 15 Copepoda. Rotifera was the dominant group in terms of quantity, and its species richness and abundance were significantly higher when compared to Cladocera and Copepoda (P < 0.05), while Cladocera dominated in terms of biomass. The species richness of Rotifera exhibited a significant seasonal difference (P < 0.05). Both the density and biomass of zooplankton revealed significant seasonal differences (P < 0.05). In general, the density and biomass of zooplankton were higher in summer and autumn, when compared to winter and spring. Biodiversity indices were dramatically lower in spring than in the other seasons. The non-metric multidimensional scaling (NMDS) analysis suggested that these zooplankton communities can be divided into three groups: spring community, summer-autumn community, and winter community. The seasonal succession of zooplankton communities did not have interannual reproducibility. In high water level years, the dominant species of zooplankton (Cladocerans and Copepods) in the wet season had a lower density, and the result in low water level years was exactly the opposite. The redundancy analysis revealed that water temperature (WT), conductivity, pH and dissolved oxygen (DO) had significant effects on the zooplankton community.

Conclusions

The community structure of zooplankton has a significant seasonal pattern, but has no interannual repeatability. In high water level years, the dominant species of zooplankton (Cladocerans and Copepods) in the wet season had a lower density, and the result in low water level years was exactly the opposite. The density, biomass and diversity indices of zooplankton were significantly different in different seasons. The present study was helpful in the further understanding of the ecosystem stability of lakes connected with rivers, providing scientific guidance for the protection of lake wetlands.
Land use management based on multi-scenario allocation and trade-offs of ecosystem services in Wafangdian County, Liaoning Province, China
Authors: Zhao Wenzhen , Han Zenglin , Yan Xiaolu , Zhong Jingqiu
Published: September 2019

Developing effective methods to coordinate the trade-offs among ecosystem services (ES) is important for achieving inclusive growth and sustainable development, and has been the focus of scholars and ecosystem managers globally. Using remote sensing and geographic information system (GIS) data, our study examined Wafangdian County of Liaoning Province as a case study to reveal the spatiotemporal evolution of four ES (food supply [FS], net primary productivity [NPP], water yield [WY], and soil conservation [SC]) and changes among their interactions. Then, an ordered weighted averaging model was introduced to simulate the optimal scenario of ES allocation. Results showed that: (1) the spatial and temporal changes in ES were significant over 14 years. All ES presented an inverted U-shaped growth curve from 2000–2014. (2) Synergies were observed within provisioning services, and there were trade-offs between provisioning services and regulating services, as well as provisioning services and supporting services. (3) The optimal scenario for Wafangdian was scenario 5 (trade-off coefficient, 0.68). The allocation of FS, NPP, WY, and SC in scenario 5 were 0.187, 0.427, 0.131, and 0.063, respectively. Implementing each ES weight of optimal scenario in land use management contributed to achieving intercoordination of ES. We propose to coordinate land and sea management to restore natural habitats that were expanded into in the high ES area. It is our anticipation that this study could provide a scientific basis for optimizing the allocation of ES and improving land use structure of coastal zones in the future.
Why the long face? Comparative shape analysis of miniature, pony, and other horse skulls reveals changes in ontogenetic growth
Authors: Heck Laura , Sanchez-Villagra Marcelo R. , Stange Madlen
Published: September 2019

Background

Much of the shape variation found in animals is based on allometry and heterochrony. Horses represent an excellent model to investigate patterns of size-shape variation among breeds that were intentionally bred for extreme small and large sizes.

Methods

We tested whether ponies (wither height < 148 cm) have a diverging size-shape relationship in skull shape as compared to regular-sized horse breeds (wither height > 148 cm, here-after called horses) during ontogenetic growth. We used a dataset of 194 specimens from 25 horse and 13 pony breeds, two of which are miniature breeds (wither height < 96.5 cm)—Falabella, Shetland. We applied three-dimensional geometric morphometrics, linear measurements, and multivariate analyses (Procrustes ANOVAs) to quantitatively examine and compare the ontogenetic trajectories between pony and horse breeds with an emphasis on the miniature breeds as an extreme case of artificial selection on size. Additionally, we tested for juvenile characteristics in adult horse and miniature breeds that could resemble “paedomorphosis”—retention of juvenile characteristics in adult stage; e.g. large eyes, large braincase-to-face-relationship, and large head-to-body relationship.

Results

Allometric regression of size on shape revealed that 42% of shape variation could be explained by variation in size in all breeds. The ontogenetic trajectories of ponies and horses vary in slope and therefore in rate of change per unit size, and length. The differences in trajectory lengths and slopes result in ponies having a similar skull shape in an older age stage than horses of the same size in a younger age stage. This pattern could cause the generally perceived “paedomorphic” appearance of ponies. Miniature breeds have larger heads in relation to wither height compared to horses, a non-paedomorphic feature in horses specifically. Also, rostra (faces) are longer in adult individuals than in juveniles across all kinds of breeds. This pattern can be explained by the long-face hypothesis for grazing ungulates and could possibly be caused by the mismatch of selection by humans for shorter rostra and the dentition of ruminants.

Conclusions

Miniature breed specimens do not exhibit any of the classical mammalian “paedomorphic” features (large orbits, large heads), except for the adult Falabella that has enlarged orbits, possibly because they are herbivorous ungulates that are affected by functional and metabolic constraints related to low nutrient-food consumption. Instead ponies, including miniature breeds, have faster and shorter ontogenetic growth compared to horses, resulting in adult pony skulls looking in part like juvenile horse skulls.
Influence of Kraal Manure, Chicken Manure and Inorganic Fertilizer on Growth, Yield and Post-harvest Quality of Pepper (Capsicum annuum L.) in a Sub-tropical Environment
Authors: Kunene Thulani R. , Masarirambi Michael T. , Wahome Paul K. , Oseni Tajudeen O.
Published: September 2019

The excessive unjustified use of some kinds of fertilizers has seen some farmers realizing poor quality fruit that does not appeal to the final consumer, thus negatively affecting the effort of alleviating poverty in the Kingdom of Eswatini. This experiment was carried out at the Horticulture Department Lath House, Faculty of Agriculture, Luyengo Campus of the University of Eswatini to determine the growth, yield and shelf-life of green pepper when fertilized with kraal manure, poultry manure and inorganic fertilizer. The experiment was conducted to find the optimum levels of fertilizers that promotes the growth of pepper and to find the effects of different fertilizers on yield and quality of pepper. The treatments included kraal manure applied at 60 t/ha, [NPK (2:3:2) 37] at 370 kg/ha, chicken manure at 40 t per hectare and the control with no amendment. The results showed that growing pepper using the four treatments significantly affected its growth rate, leaf number, fruit number and its (fruit) shelf life. Pepper grown using inorganic fertilizer had the highest leaf number followed in decreasing order by chicken manure, kraal manure and lastly peppers which did not receive any amendment.  There were no significant difference in the growth rate of pepper in the inorganic fertilizer and chicken manure treatments. Similarly, there was no significant difference of pepper grown with chicken manure and chemical fertilizer in the number of days it took the harvested pepper to reach 100% decay stored at room temperature for 21 days. Yet pepper grown with kraal manure was significantly different from the two as it showed 20% decay rate in the same number of days. Although the control had the least decay, the yield was the lowest thus it is not recommended. Kraal manure at 60 t/ha is recommended in the production of pepper with a longer shelf life.
Energy Potential Study of Some Tropical Wood Species from Nigeria
Authors: Asibor J. O. , Akhator E. P. , Obanor A. I.
Published: September 2019

Aims: To carry out experimental study of the energy potential of some tropical wood species.

Study Design: It involved sample collection, experimental analysis and numerical validation of the obtained calorific values.

Place and Duration of Study: National Centre for Energy Research and Development (NCERD), University of Nigeria, Nsukka, Enugu State, Nigeria between November 2016 and September 2018.

Methodology: Wood waste (saw dust) from ten (10) selected tropical wood species sourced from sawmills in Benin City, Nigeria were subjected to proximate analysis, ultimate analysis as well as energy content study.

Results: Thermal conversion characteristics of low ash content (0.2 – 2.76%), very high volatile matter (87.51 – 90.94%), low moisture content (8.62 – 10.53%.), relatively high carbon, hydogen and oxygen contents as well as low nitrogen and sulphur contents were observed. Obtained calorific values were validated using three already existing correlations.

Conclusion: Among the 10 species studied, Afzelia africana (Apa) was found to be best suited for energy generation while Triplocyton scleroxylon (Obeche) was found to be least suited.
Time to Command-Following and Outcomes After Traumatic Brain Injury
Authors: Snider Samuel B. , Deng Hansen , Hammond Flora M. , Kowalski Robert G. , Walker William C. , Zafonte Ross D. , Okonkwo David O. , Giacino Joseph T. , Puccio Ava M. , Bodien Yelena G.
Published: December 2024

This cohort study examines the association of time to command-following with death or dependency at 1 year among individuals with moderate-severe traumatic brain injury (TBI).
Procedure Coding, Reimbursement, and Billing Compliance
Authors: Baselski Vickie S. , Weissfeld Alice S.
Published: December 2024

Correct procedure coding is the foundation for accurate documentation of services for workload productivity determination in addition to accurate billing and reimbursement for services and is a critical element of a laboratory compliance program. This chapter discusses factors to be considered in code selection. Several code types are used for microbiology services. These include: CPT codes, HCPCS codes, and other procedure coding systems. Microbiology coding is based on methodological approaches in the laboratory and falls into several categories. Billing for laboratory test procedures occurs via several different mechanisms. The primary billing mechanisms include the following: retrospective payment, prospective payment, new technology add‐on payments, and value‐based payments. The primary role for the laboratory in reimbursement is to ensure that correct coding has been applied to services rendered so that appropriate billing and workload documentation occurs.
Introduction
Authors: Harrington Amanda T. , Yarbrough Melanie L.
Published: December 2024

The aerobic bacteriology encompasses procedures used for the culture of aerobic and facultative anaerobic bacteria that are routinely recovered from human clinical specimens as well as specialized procedures for more fastidious organisms. This chapter reflects common associations between selected organisms at a particular site of infection. Each procedure provides information on isolation and recognition of these bacteria as well as their clinical relevance. The chapter concludes with procedures for rapid and streamlined identification of many common and important aerobic bacteria. While the tables and flowcharts in these procedures are designed to identify clinically important microorganisms using minimal phenotypic testing, in many cases, additional testing is needed for a specific species‐level identification. With the application of newer technologies such as total laboratory automation and artificial intelligence processes procedures for recovery and identification of aerobic bacteria within the clinical microbiology laboratory will continue to evolve.
Body Fluid Cultures (Excluding Blood, Cerebrospinal Fluid, and Urine)
Authors: Moore Nicholas M.
Published: December 2024

Infection of normally sterile body fluids often results in severe morbidity and mortality; therefore, rapid and accurate microbiological assessment of these samples is important for successful patient management. Care must be taken during specimen collection and transport to ensure that the specimen is not contaminated. Causes of prosthetic joint infection vary depending on the joint infected and the time between implantation and infection. Peritoneal fluid can be contaminated with numerous mixed gastrointestinal (GI) microbiota in cases of perforation of the GI tract, but in patients with peritonitis secondary to continuous ambulatory peritoneal dialysis (CAPD) or spontaneous bacterial peritonitis, the likely pathogen may be present in very low numbers. In peritonitis secondary to CAPD, the typical pathogens are staphylococci; viridans group streptococci; non‐glucose‐fermenting, Gram‐negative bacilli;
Candida albicans
and other
Candida
spp.; and fungi.
Leptospira
Culture
Authors: Galloway Renee L.
Published: December 2024

Leptospirosis is a zoonosis caused by spirochetes of the genus
Leptospira
.
Leptospira
serovars that are antigenically related are further grouped into serogroups, primarily to simplify serologic diagnosis. Infection with
Leptospira
in humans may result in a wide spectrum of symptoms, ranging from mild, undifferentiated febrile illness to severe multiorgan system disease, with jaundice, renal failure, cardiac complications, severe pulmonary hemorrhagic syndrome, and high mortality. Clinical recognition of leptospirosis is difficult because leptospires can affect many different organ systems, resulting in a nonspecific clinical presentation. Consequently, leptospirosis is often misdiagnosed as influenza, malaria, aseptic meningitis, encephalitis, dengue fever, hepatitis, or gastroenteritis. Direct dark‐field smears are not recommended for leptospirosis diagnosis due to their lack of sensitivity. Leptospires are aerobic bacteria that can be cultivated at 30 degree Celsius in media containing either rabbit serum or bovine serum albumin and fatty acids.
Identification of Gram‐Negative Bacteria
Authors: Munson Erik , Podzorski Raymond P.
Published: December 2024

The Gram‐negative bacteria are a heterogeneous group of organisms consisting of numerous families, genera, and species, many of which cause serious disease and endotoxic shock. The accurate, rapid identification of Gram‐negative bacilli, coccobacilli, and diplococci makes it possible to provide timely, meaningful treatment and diagnosis of disease. Commercial kit‐based identification systems do an excellent job of identifying most pathogens with minimal work and are often a major tool in the laboratory's identification system. Deciding when to use a commercial system and which system to use for identification is key to success in providing the identification in a timely manner. The speed of identification and extremely low reagent cost make the technology a desirable means of organism identification in the clinical microbiology setting. In the course of the potential rapid identification of Gram‐negative coccobacilli and Gram‐negative bacilli, the clinical microbiology laboratory may encounter isolates that are potential agents of bioterrorism.
Commercial Kit and Rapid Enzymatic Systems for the Identification of Anaerobes
Authors: Valencia‐Shelton Frances , Bard Jennifer Dien
Published: December 2024

Biochemical systems for identification of anaerobes rely on the metabolic breakdown of substrates and the production of end products during the growth of the isolated organism. There is currently one commercially packaged kit system that uses this method for the identification of commonly isolated anaerobic bacteria in the clinical microbiology laboratory: the API 20A system. The API 20A requires overnight incubation, whereas rapid identification of anaerobes can be accomplished with commercially available microsystems that detect preformed enzymes of isolate suspension within a few hours. Database and numerical identification profiles are provided by the manufacturer for each system. Identification of anaerobes to the species level was reported at 74% with rapid enzymatic systems, compared to 50% with API 20A. The use of rapid methods such as matrix‐assisted laser desorption ionization–time‐of‐flight mass spectrometry has certainly replaced biochemicals and enzymatic reactions in many laboratories.
Anaerobic Cocci
Authors: She Rosemary C. , Church Deirdre L.
Published: December 2024

The anaerobic cocci are a prominent part of the normal human microbiota of the skin, gastrointestinal tract, oral cavity, upper respiratory tract, and female genital tract. Gram‐positive anaerobic cocci (GPAC) can be important human pathogens, and next to the Gram‐negative anaerobic bacilli (GNAC), these anaerobes are the most isolated in clinically relevant infections. Anaerobic cocci recovered in isolation from specimens obtained from specific types of invasive infections and specimen types should be fully identified to the genus and often species level. Anaerobic cocci isolated from blood cultures, other sterile fluids, deep organ tissues, deep wounds, or abscesses may particularly be fully analyzed to aid clinical management. Anaerobic cocci can be identified by Gram stain, colonial morphology, rapid tests, and various biochemical reactions, in tube or kit systems.
Finegoldia magna
is the most predominant pathogen among the GPAC and can be solely responsible for several different types of infections.
Preanalytical Considerations and Laboratory Processing of Samples for Blood Culture
Authors: Tibbetts Robert J. , Harrington Amanda T.
Published: December 2024

This chapter presents the preanalytical considerations and laboratory processing of samples for blood culture. Bloodstream infection and sepsis remain one of the most significant causes of morbidity and mortality worldwide. Establishing an etiologic diagnosis for bloodstream infections is an essential role of clinical microbiology laboratories. The number of blood culture bottles collected and the volume of blood collected in each bottle also significantly impact recovery of organisms and interpretation of results. The volume of blood obtained for culture is typically determined using an age‐ or weight‐based calculation. Adequate volume of blood is the single most important factor in the laboratory detection of microorganisms in the bloodstream, regardless of age; when blood culture is optimized to the recommended volumes, the more likely a culture will be positive. Blood culture collection prior to administration of antimicrobials is essential for optimal organism recovery.
Broad‐Range PCR and Emerging Technologies for the Direct Detection of Microorganisms from Blood Specimens
Authors: Green Daniel A.
Published: December 2024

Broad‐range PCR methods that amplify and sequence the 16S rRNA gene have been used for bacterial identification both from blood culture bottles and directly from whole blood. Applied to residual positive blood culture broth, broad‐range PCR has been shown to increase the detection of clinically significant bacteria when combined with routine culture, although higher rates of contaminating organisms may also be detected. Broad‐range PCR has also been demonstrated to have high concordance with conventional blood culture when performed on blood culture bottles incubated for 8 h prior to analysis. Multiple studies have evaluated the use of broad‐range PCR directly from whole blood samples. While blood culture remains the gold standard for the diagnosis of bloodstream infections, its sensitivity is influenced by several variables, including the volume of blood collected, the timing of blood collection, and the growth characteristics of the microorganism(s).
Introduction
Authors: McElvania Erin
Published: December 2024

There has been a revolution in the way clinical microbiology laboratories identify microorganisms with the advent of matrix‐assisted laser desorption ionization–time of flight mass spectrometry (MALDI‐TOFMS). MALDI‐TOFMS identifies microorganisms based on their protein profile rather than traditional methods of phenotypic identification such as biochemical testing. MALDI‐TOFMS identification begins with colonies growing on solid agar or growing in liquid media. Cellular extracts of microorganism or direct application of a thin layer of organism from a colony are applied to the MALDI‐TOFMS target, followed by the application of matrix. Initial use of MALDI‐TOF in the clinical microbiology laboratory focused on bacterial identification from colonies growing on solid agar. Due to the ease of use, cost savings, and high accuracy, many laboratories had interest in using MALDI‐TOFMS for identification of other organism groups.
Introduction to Antimicrobial Susceptibility Testing Methods
Authors: Humphries Romney M. , Simner Patricia J.
Published: December 2024

Antimicrobial susceptibility testing (AST) is arguably one of the most important roles that clinical microbiology laboratories play, especially in the era of increasing antimicrobial resistance. Several conventional and novel methods are available to perform AST. Traditional quantitative AST methods, such as broth dilution, gradient diffusion, and agar dilution, and automated broth microdilution instruments generate a MIC. Disk diffusion is a method reported qualitatively that generates a zone diameter that is inversely related to the MIC. This chapter describes the different types of phenotypic antimicrobial susceptibility tests, with reference to the methods in CMPH. Breakpoints are based on robust clinical, pharmacokinetic/pharmacodynamic, and microbiological data in order to provide a reasonable prediction of clinical outcome for an infection treated with a given antimicrobial agent.
Agar Dilution MIC Test
Authors: Patel Samir N.
Published: December 2024

The agar dilution MIC test is a quantitative method for the determination of in vitro activity of an antimicrobial agent against bacterial isolates, such as aerobic and anaerobic bacteria. Following incubation using conditions appropriate for the test organisms, the MIC is determined by observing the lowest concentration of antimicrobial agent that inhibits visible growth of each test isolate. MICs obtained are interpreted as susceptible, intermediate, susceptible dose‐dependent, resistant, or non‐susceptible based on criteria defined by the CLSI or by the European Committee on Antimicrobial Susceptibility Testing. Recommendations for performance of the agar dilution method for susceptibility testing of aerobic bacteria are found in the CLSI M07 standard and include procedures for both non‐fastidious and fastidious organisms. The chapter covers proper quality control principles for analytical tests. With postanalytical considerations, it provides attention to common test limitations, interpretive challenges, and results reporting.
Tularemia—
Francisella tularensis
Authors: Schaecher Kurt E.
Published: December 2024

Francisella tularensis
is a fastidious, tiny, Gram‐negative coccobacillus and the etiological agent of tularemia.
F. tularensis
is a known risk for laboratory‐acquired infection. The identification of
F. tularensis
should not be attempted with commercial identification systems because of the potential of generating aerosols and the high probability of misidentification.
F. tularensis
is widespread throughout the Northern Hemisphere and is responsible for recent tularemia outbreaks in several countries, including Norway and Turkey.
F. tularensis
is a zoonotic pathogen with an extremely wide host range that includes mammals, birds, and amphibians. The primary hosts for
F. tularensis
are believed to be small rodents (hares, voles, muskrats).
F. tularensis
was actively pursued as a biological warfare agent by both the United States and the former Soviet Union.
Melioidosis (
Burkholderia pseudomallei
) and Glanders (
Burkholderia mallei
)
Authors: Egan Christina , Perry Michael J.
Published: December 2024

Burkholderia mallei
is the etiologic agent of glanders, a febrile illness typically seen in equines, i.e., horses, mules, and donkeys. It is a nonmotile, aerobic Gram‐negative coccobacillus, which may or may not be oxidase positive or grow on MacConkey agar.
Burkholderia pseudomallei
was thought to cause a glanders‐like illness in humans.
B. pseudomallei
is an oxidase‐positive, aerobic Gram‐negative bacillus that is straight or slightly curved. The recent sequencing of the genomes suggests that
B. mallei
is a recently evolved clone of
B. pseudomallei
.
B. mallei
infections can present either as cutaneous or systemic. The chapter covers safety considerations, materials, specimen collection, and quality control principles for preanalytical considerations. For analytical considerations, it provides specimen processing, incubation and examination of cultures, and culture identification. With postanalytical considerations, the chapter also provides attention to common test limitations, interpretive challenges, and results reporting.
Linking Nanoscopic Insights to Millimetric‐Devices in Formamidinium‐Rich Perovskite Photovoltaics
Authors: Othman Mostafa , Jeangros Quentin , Rothmann Mathias Uller , Jiang Yang , Ballif Christophe , Hessler‐Wyser Aïcha , Wolff Christian M.
Published: December 2024

Halide‐perovskite semiconductors have a high potential for use in single‐junction and tandem solar cells. Despite their unprecedented rise in power conversion efficiencies (PCEs) for photovoltaic (PV) applications, it remains unclear whether perovskite solar modules can reach a sufficient operational lifetime. In order to make perovskite solar cells (PSCs) commercially viable, a fundamental understanding of the relationship between their nanostructure, optoelectronic properties, device efficiency, and long‐term operational stability/reliability needs to be established. In this review, the phase instabilities in state‐of‐the‐art formamidinium (FA)‐rich perovskite absorbers is discussed. Furthermore, the concerted efforts are summarized in this prospect, covering aspects from fundamental research to device engineering. Subsequently, a critical analysis of the dictating impact of the nanoscale landscape of perovskite materials on their resulting intrinsic stability is provided. Finally, the remaining challenges in the field are assessed and future research directions are proposed for improving the operational lifetimes of perovskite devices. It is believed that these approaches, which bridge nanoscale structural properties to working solar cell devices, will be critical to assessing the realization of a bankable PSC product.
Synergistic Acid‐Base Action Leads to Ultrafast Decontamination of Nerve and Blister Agents by OH− Intercalated Zr4+‐Doped MgAl‐LDH under Ambient Conditions
Authors: Huang Chengcheng , Yang Ying , Wang Pingjing , Fu Hongchen , Hu Xin , Zhou Yunshan , Zhang Lijuan , Zhong Yuxu
Published: December 2024

Developing materials capable of rapidly decontaminating nerve and blister agents directly under ambient conditions are crucial for practical applications. In this work, Mg3Al1‐xZrx‐LDH with different Zr4+ doping contents and corresponding OH− intercalated materials Mg3Al1‐xZrx‐LDH‐OH are synthesized. First, they are used for the decontamination of nerve agents under ambient conditions, showing that increasing the Zr4+ doping amount accelerates the decontamination rate of diethyl cyanophosphonate (DECP) and soman (GD), with the half‐life of DECP and GD being 3–5 times shorter with Mg3Al0.6Zr0.4‐LDH (the highest Zr4+ doping content) compared to Mg3Al1‐LDH. Notably, the intercalation of OH− in Mg3Al0.6Zr0.4‐LDH further greatly enhances the catalytic activity for DECP and GD, the reaction half‐life of DECP and GD with Mg3Al0.6Zr0.4‐LDH‐OH being 18 s and <15 s, respectively, which is the shortest recorded so far. Additionally, under ambient conditions, Mg3Al0.6Zr0.4‐LDH‐OH exhibits superior detoxification performance for mustard gas (HD) compared to Mg3Al0.6Zr0.4‐LDH, with 92.8% of HD being removed within 6 h. Mechanistic studies reveal that Mg3Al0.6Zr0.4‐LDH‐OH efficiently decontaminates nerve and blister agents utilizing the synergistic effect of Lewis acid‐base sites (Zr4+ and laminate OH groups) and interlayer OH−. To extend the practical applications of the materials, PVA@(PAN/LDH‐OH) self‐detoxifying fiber loaded with Mg3Al0.6Zr0.4‐LDH‐OH is prepared.
Simultaneous Regulating the Surface, Interface, and Bulk via Phosphating Modification for High‐Performance Li‐Rich Layered Oxides Cathodes
Authors: Lou Yuhang , Lin Zedong , Shen Jialong , Sun Junpeng , Wang Nan , Chen Zhihao , Huang Rong , Rui Xianhong , Wu Xiaojun , Yang Hai , Yu Yan
Published: December 2024

Li‐rich Mn‐based layered oxides (LRMOs) are regarded as the leading cathode materials to overcome the bottleneck of higher energy density. Nevertheless, they encounter significant challenges, including voltage decay, poor cycle stability, and inferior rate performance, primarily due to irreversible oxygen release, transition metal dissolution, and sluggish transport kinetics. Moreover, traditionally single modification strategies do not adequately address these issues. Herein, an innovative “all‐in‐one” modification strategy is developed, simultaneously regulating the surface, interface, and bulk via an in‐situ gas–solid interface phosphating reaction to create P‐doped Li1.2Mn0.54Ni0.13Co0.13O2@Spinel@Li3PO4. Specifically, Li3PO4 surface coating layer shields particles from electrolyte corrosion and enhances Li+ diffusion; in‐situ constructed spinel interfacial layer reduces phase distortion and suppresses the lattice strain; the strong P─O bond derived from P‐doping stabilizes the lattice oxygen frame and inhibits the release of O2, thereby improving the reversibility of oxygen redox reaction. As a result, the phosphatized LRMO demonstrates an exceptional capacity retention of 82.1% at 1C after 300 cycles (compared to 50.8% for LRMO), an outstanding rate capability of 170.5 mAh g−1 at 5C (vs 98.9 mAh g−1 for LRMO), along with excellent voltage maintenance and thermostability. Clearly, this “all‐in‐one” modification strategy offers a novel approach for high‐energy‐density lithium‐ion batteries.
PNPO‐Mediated Oxidation of DVL3 Promotes Multiple Myeloma Malignancy and Osteoclastogenesis by Activating the Wnt/β‐Catenin Pathway
Authors: Deng Zhendong , Sun Shanliang , Zhou Nian , Peng Yumeng , Cheng Long , Yu Xichao , Yuan Yuxia , Guo Mengjie , Xu Min , Cheng Yuexin , Zhou Fan , Li Nianguang , Yang Ye , Gu Chunyan
Published: December 2024

Multiple myeloma (MM) is a cancer of plasma cells caused by abnormal gene expression and interactions within the bone marrow (BM) niche. The BM environment significantly influences the progression of MM. Celastrol, a natural compound derived from traditional Chinese medicine, exhibits significant anticancer effects. This study aimed to identify specific targets of celastrol and develop more effective and less toxic treatment options for MM. Celastrol is used as a probe to determine its specific target, pyridoxine‐5′‐phosphate oxidase (PNPO). Increased levels of PNPO are associated with poor outcomes in MM patients, and PNPO promotes MM cell proliferation and induces osteoclast differentiation through exosomes. Mechanistically, PNPO oxidizes disheveled 3M282 (DVL3), leading to abnormal activation of the Wnt/β‐catenin pathway. Based on the critical sites of PNPOR95/K117, Eltrombopag is identified as a potential therapeutic candidate for MM. In addition, the experiments showed its efficacy in mouse models. Eltrombopag inhibited the growth of MM cells and reduced bone lesions by disrupting the interaction between PNPO and DVL3, as supported by preliminary clinical trials. The study highlights the importance of PNPO as a high‐risk gene in the development of MM and suggests that Eltrombopag may be a promising treatment option.
Enhanced Oxidative Phosphorylation Driven by TACO1 Mitochondrial Translocation Promotes Stemness and Cisplatin Resistance in Bladder Cancer
Authors: Deng Minhua , Zhou Zhaohui , Chen Jiawei , Li Xiangdong , Liu Zefu , Ye Jingwei , Wei Wensu , Wang Ning , Peng Yulu , Luo Xin , Jiang Lijuan , Zhou Fangjian , Zheng Xianchong , Liu Zhuowei
Published: December 2024

Chemoresistance poses a critical obstacle in bladder cancer (BCa) treatment, and effective interventions are currently limited. Elevated oxidative phosphorylation (OXPHOS) has been linked to cancer stemness, a determinant of chemoresistance. However, the mechanisms underlying increased OXPHOS during cancer cell chemoresistance remain unclear. This study revealed that the mitochondrial translational activator of cytochrome oxidase subunit 1 (TACO1) is linked to stemness and cisplatin resistance in BCa cells. Mechanistically, mitochondrial TACO1 enhances the translation of the mitochondrial cytochrome c oxidase I (MTCO1), promoting mitochondrial reactive oxygen species (mtROS) by upregulating OXPHOS, consequently driving cancer stemness and cisplatin resistance. Intriguingly, the mitochondrial translocation of TACO1 is mediated by the heat shock protein 90 β (HSP90β), a process that requires circFOXK2 as a scaffold for the TACO1‐HSP90β interaction. The mutations at the binding sites of TACO1‐circFOXK2‐HSP90β disturb the ternary complex and inhibit cancer stemness and cisplatin resistance in BCa cells by suppressing the MTCO1/OXPHOS/mtROS axis. Clinically, BCa patients with increased mitochondrial TACO1 expression respond poorly to cisplatin treatment. This study elucidates the mechanisms by which TACO1 promotes BCa stemness and cisplatin resistance, providing a potential target for mitigating cisplatin resistance for BCa and a biomarker for predicting cisplatin response.
BRD8 Guards the Pluripotent State by Sensing and Maintaining Histone Acetylation
Authors: Sun Li , Fu Xiuling , Xiao Zhen , Ma Gang , Zhou Yibin , Hu Haoqing , Shi Liyang , Li Dongwei , Jauch Ralf , Hutchins Andrew Paul
Published: December 2024

Epigenetic control of cell fates is a critical determinant to maintain cell type stability and permit differentiation during embryonic development. However, the epigenetic control mechanisms are not well understood. Here, it is shown that the histone acetyltransferase reader protein BRD8 impairs the conversion of primed mouse EpiSCs (epiblast stem cells) to naive mouse ESCs (embryonic stem cells). BRD8 works by maintaining histone acetylation on promoters and transcribed gene bodies. BRD8 is responsible for maintaining open chromatin at somatic genes, and histone acetylation at naive‐specific genes. When Brd8 expression is reduced, chromatin accessibility is unchanged at primed‐specific genes, but histone acetylation is reduced. Conversely, naive‐specific genes has reduced repressive chromatin marks and acquired accessible chromatin more rapidly during the cell type conversion. It is shown that this process requires active histone deacetylation to promote the conversion of primed to naive. This data supports a model for BRD8 reading histone acetylation to accurately localize the genome‐wide binding of the histone acetyltransferase KAT5. Overall, this study shows how the reading of the histone acetylation state by BRD8 maintains cell type stability and both enables and impairs stem cell differentiation.
Dual‐Enhanced SERS Satellite Immuno‐Nanocomplex for Multiple PSA‐Mediated PHI Assay Toward Clinical Prostate Cancer Screening
Authors: Chen Dong , Ma Yilin , Yang Annan , Hu Liping , Zhou Hanlin , Xu Jun , Chen Shanze , Nie Dingmeng , Feng Weifeng , Cai Huaihong , Cong Yanguang , Pi Jiang , Rao Lang , Huang Xueqin , Sun Pinghua , Zhou Haibo
Published: December 2024

Prostate specific antigen (PSA) is widely used in liquid biopsy of prostate cancer (PCa) but still faces challenges due to the poor specificity. Herein, this study reports a double‐SERS satellite immunoassay, made of an Au–Ag dealloyed intra‐nanogap nanoflower (Au–Ag DINF) with strong SERS signals and Au magnetic nanoparticles (AuMNPs) with magnetic capture and SERS amplification, for sensing multiple PSA (free PSA (fPSA), complexed PSA (cPSA) and [‐2]proPSA (p2PSA)) toward potential PCa screening. Unlike the previous studies focus on the tPSA and fPSA/tPSA ratio (f/t PSA%), this work introduces a multiple PSA‐mediated Prostate Health Index (PHI) assay with significantly increased the predictive accuracy and specificity of PCa, especially the patients with a tPSA level in the “diagnostic gray zone”. Practical analysis of clinical samples demonstrated the SERS immunoassay is capable of identifying the PCa subjects from healthy candidates (N = 13), and monitoring PCa patients before and after surgery (N = 5), as well as screening suspicious ones who are in the “gray zone” (N = 10). Overall, benefiting from the PSA‐responsive satellite immuno‐nanoassemble strategy, dual‐SERS magnification effect, and multiple PSA‐based PHI assessment, this proposes bioassay held enormous potential for the early diagnosis, screening, monitoring, and prognosis of PCa.
Hydrogen‐Generating Magnesium Alloy Seed Strand Sensitizes Solid Tumors to Iodine‐125 Brachytherapy
Authors: Hu Pan , Lin Letao , Chen Guanyu , Liu Dengyao , Guo Huanqing , Xiao Meigui , Zhong Zhihui , Yang Guang , Xu Bingchen , Huang Dongcun , Peng Sheng , Li Yong , Zhang Yanling , Huang Tao , Zhang Fujun
Published: December 2024

Radioactive iodine‐125 (125I) seed implantation, a brachytherapy technique, effectively kills tumor cells via X‐rays and gamma rays, serving as an alternative therapeutic option following the failure of frontline treatments for various solid tumors. However, tumor radioresistance limits its efficacy. Hydrogen gas has anticancer properties and can enhance the efficacy of immunotherapy. However, its role in radiotherapy sensitization has rarely been reported. Many current hydrogen delivery methods involve hydrogen‐generating nanomaterials, such as magnesium‐based nanomaterials. This study introduces an AZ31 magnesium alloy 125I seed strand (termed AMASS) with pH‐dependent slow‐release hydrogen characteristics and excellent mechanical properties. AMASS can be implanted into tumors via minimally invasive surgery, releasing hydrogen around the 125I seeds. In vitro experiments showed that hydrogen from AMASS degradation significantly inhibited tumor proliferation, increased apoptosis, disrupted redox homeostasis and mitochondrial membrane potential, reduced adenosine triphosphate levels, and induced DNA damage due to 125I radiation. In mouse xenograft and rabbit liver tumor models, hydrogen from AMASS showed superior therapeutic effects compared with 125I seeds alone, with no noticeable side effects. In addition, AMASS has a uniform radiation dose distribution and simple implantation. Therefore, hydrogen from AMASS enhanced 125I seed efficacy, supporting the further promotion and application of 125I seed implantation in cancer therapy.
CDC20‐Mediated Selective Autophagy Degradation of PBRM1 Affects Immunotherapy for Renal Cell Carcinoma
Authors: Fan Yizeng , Dan Weichao , Que Taotao , Wei Yi , Liu Bo , Wang Zixi , Zhang Yulin , Wang Yuzhao , Liu Tianjie , Zhuang Yanxin , Li Mengxing , Guo Chendong , Zeng Jin , Ma Bohan , Li Lei
Published: December 2024

Polybromo 1 (PBRM1) inactivating mutations are associated with clinical benefit from immune checkpoint inhibitor treatments in clear cell renal cell carcinoma (ccRCC). However, whether targeting PBRM1 has the potential to enhance immunotherapy efficacy in patients with wild‐type PBRM1 and the upstream pathways that regulate PBRM1 protein stability remain unclear. Here, it is demonstrated that PBRM1 knockdown induced M1 macrophage polarization and infiltration, which enhanced the efficacy of anti‐PD‐1 immunotherapy in RCC. Meanwhile, CDC20 catalyzes K27 ubiquitination of PBRM1 and promotes its degradation via p62‐mediated selective autophagy. A bicyclic peptide (PB1‐p62) is designed and constructed to target PBRM1 and p62, thereby promoting the degradation of PBRM1. As a result, the efficacy of anti‐PD‐1 immunotherapy is enhanced, leading to improved overall survival rates in syngeneic mouse tumor models. Overall, this finding suggest the clinical application of PB1‐p62 and provide a novel approach for enhancing the effectiveness of immunotherapy in RCC patients with wild‐type PBRM1.
Dual Inhibition of CDK4/6 and CDK7 Suppresses Triple‐Negative Breast Cancer Progression via Epigenetic Modulation of SREBP1‐Regulated Cholesterol Metabolism
Authors: Yang Yilan , Liao Jiatao , Pan Zhe , Meng Jin , Zhang Li , Shi Wei , Wang Xiaofang , Zhang Xiaomeng , Zhou Zhirui , Luo Jurui , Chen Xingxing , Yang Zhaozhi , Mei Xin , Ma Jinli , Zhang Zhen , Jiang Yi‐Zhou , Shao Zhi‐Min , Chen Fei Xavier , Yu Xiaoli , Guo Xiaomao
Published: December 2024

Inhibitors targeting cyclin‐dependent kinases 4 and 6 (CDK4/6) to block cell cycle progression have been effective in treating hormone receptor‐positive breast cancer, but triple‐negative breast cancer (TNBC) remains largely resistant, limiting their clinical applicability. The study reveals that transcription regulator cyclin‐dependent kinase7 (CDK7) is a promising target to circumvent TNBC's inherent resistance to CDK4/6 inhibitors. Combining CDK4/6 and CDK7 inhibitors significantly enhances therapeutic effectiveness, leading to a marked decrease in cholesterol biosynthesis within cells. This effect is achieved through reduced activity of the transcription factor forkhead box M1 (FOXM1), which normally increases cholesterol production by inducing SREBF1 expression. Furthermore, this dual inhibition strategy attenuates the recruitment of sterol regulatory element binding transcription factor 1 (SREBP1) and p300 to genes essential for cholesterol synthesis, thus hindering tumor growth. This research is corroborated by an in‐house cohort showing lower survival rates in TNBC patients with higher cholesterol production gene activity. This suggests a new treatment approach for TNBC by simultaneously targeting CDK4/6 and CDK7, warranting additional clinical trials.