bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Investigation of Rotor Vibration Induced by Rotor-Stator Rubbing With Soft Coating
Authors: Ma Ruixian , Lei Xinliang , Wang Wen , Liao Mingfu
Published: August 2024

Rotor-stator rubbing is common in aero-engines, and the resulting vibration characteristic is affected by the coating material and the structure of rotor and stator. Partial rubbing between a soft rubber coated casing and seal labyrinth teeth on a thin-shell rotating drum is investigated. The vibration response of the drum and the rear end of the rotor is analyzed from the perspective of time, frequency and hologram domains. The time waveform of the drum is significantly distorted by rubbing, resulting in strong fluctuations of the vibration amplitude. The rubbing is observed within a very short time, followed by recovery of stable vibration of the rotor. Rotor-stator coupling vibration is excited by this studied rubbing. The natural frequencies corresponding to the pith diameter vibration modes both of the drum and the casing can be observed in the vibration spectrums of the drum. The synchronous forward whirl is suppressed to some extend by rubbing, whereas the synchronous backward whirl is enhanced. The smaller the whirl amplitude ratio between the forward whirl and backward whirl, the more serious the rubbing. The vibration at the rotor rear end is hardly affected.
Chiral edge waves in a dance-based human topological insulator
Authors: Du Matthew , Pérez-Sánchez Juan B. , Campos-Gonzalez-Angulo Jorge A. , Koner Arghadip , Mellini Federico , Pannir-Sivajothi Sindhana , Poh Yong Rui , Schwennicke Kai , Sun Kunyang , van den Wildenberg Stephan , Karzen Dylan , Barron Alec , Yuen-Zhou Joel
Published: August 2024

Topological insulators are insulators in the bulk but feature chiral energy propagation along the boundary. This property is topological in nature and therefore robust to disorder. Originally discovered in electronic materials, topologically protected boundary transport has since been observed in many other physical systems. Thus, it is natural to ask whether this phenomenon finds relevance in a broader context. We choreograph a dance in which a group of humans, arranged on a square grid, behave as a topological insulator. The dance features unidirectional flow of movement through dancers on the lattice edge. This effect persists when people are removed from the dance floor. Our work extends the applicability of wave physics to dance.
Boosting spatial and energy resolution in STM with a double-functionalized probe
Authors: Odobesko Artem , Klees Raffael L. , Friedrich Felix , Hankiewicz Ewelina M. , Bode Matthias
Published: August 2024

The scattering of superconducting pairs by magnetic impurities on a superconducting surface leads to pairs of sharp in-gap resonances known as Yu-Shiba-Rusinov (YSR) bound states. Similar to the interference of itinerant electrons scattered by defects in normal metals, these resonances reveal a periodic texture around the magnetic impurity. The wavelength of these resonances is, however, often too short to be resolved even by methods capable of atomic resolution, i.e., scanning tunneling microscopy (STM). We combine a CO molecule with a superconducting cluster pre-attached to an STM tip to maximize both spatial and energy resolution, thus demonstrating the superior properties of such double-functionalized probes by imaging the spatial distribution of YSR states. Our approach reveals rich interference patterns of the hybridized YSR states of two Fe atoms on Nb(110), previously inaccessible with conventional STM probes. This advancement extends the capabilities of STM techniques, providing insights into superconducting phenomena at the atomic scale.
Extending computational protein design to intrinsically disordered proteins
Authors: Robustelli Paul
Published: August 2024

Advances in the accuracy and throughput of molecular simulations usher in a new era in the structural biology of disordered proteins.
Next-generation CAR T cell therapies for glioblastoma
Authors: Bernstock Joshua D. , Gerstl Jakob V. E. , Valdés Pablo A. , Friedman Gregory K. , Chiocca E.
Published: August 2024

Interim results from two phase 1 trials demonstrate progress in the use of chimeric antigen receptor (CAR) T cell therapy for recurrent glioblastoma (GBM).
IncC plasmid genome rearrangements influence the vertical and horizontal transmission tradeoff in
Escherichia coli
Authors: Allain Margaux , Morel-Journel Thibaut , Condamine Bénédicte , Gibeaux Benoist , Gachet Benoit , Gschwind Rémi , Denamur Erick , Landraud Luce
Published: August 2024

It has been shown that an evolutionary tradeoff between vertical (host growth rate) and horizontal (plasmid conjugation) transmissions contributes to global plasmid fitness. As conjugative IncC plasmids are important for the spread of multidrug resistance (MDR), in a broad range of bacterial hosts, we investigated vertical and horizontal transmissions of two multidrug-resistant IncC plasmids according to their backbones and MDR-region rearrangements, upon plasmid entry into a new host. We observed plasmid genome deletions after conjugation in three diverse natural
Escherichia coli
clinical strains, varying from null to high number depending on the plasmid, all occurring in the MDR region. The plasmid burden on bacterial fitness depended more on the strain background than on the structure of the MDR region, with deletions appearing to have no impact. Besides, we observed an increase in plasmid transfer rate, from ancestral host to new clinical recipient strains, when the IncC plasmid was rearranged. Finally, using a second set of conjugation experiments, we investigated the evolutionary tradeoff of the IncC plasmid during the critical period of plasmid establishment in
E. coli
K-12, by correlating the transfer rates of deleted or non-deleted IncC plasmids and their costs on the recipient strain. Plasmid deletions strongly improved conjugation efficiency with no negative growth effect. Our findings indicate that the flexibility of the MDR-region of the IncC plasmids can promote their dissemination, and provide diverse opportunities to capture new resistance genes. In a broader view, they suggest that the vertical-horizontal transmission tradeoff can be manipulated by the plasmid to improve its fitness.
A growth-based screening strategy for engineering the catalytic activity of an oxygen-sensitive formate dehydrogenase
Authors: Li Feilong , Scheller Silvan , Lienemann Michael
Published: August 2024

Enzyme engineering is a powerful tool for improving or altering the properties of biocatalysts for industrial, research, and therapeutic applications. Fast and accurate screening of variant libraries is often the bottleneck of enzyme engineering and may be overcome by growth-based screening strategies with simple processes to enable high throughput. The currently available growth-based screening strategies have been widely employed for enzymes but not yet for catalytically potent and oxygen-sensitive metalloenzymes. Here, we present a screening system that couples the activity of an oxygen-sensitive formate dehydrogenase to the growth of
Escherichia coli
. This system relies on the complementation of the
E. coli
formate hydrogenlyase (FHL) complex by Mo-dependent formate dehydrogenase H (
Ec
FDH-H). Using an
Ec
FDH-H-deficient strain, we demonstrate that growth inhibition by acidic glucose fermentation products can be alleviated by FHL complementation. This allows the identification of catalytically active
Ec
FDH-H variants at a readily measurable cell density readout, reduced handling efforts, and a low risk of oxygen contamination. Furthermore, a good correlation between cell density and formate oxidation activity was established using
Ec
FDH-H variants with variable catalytic activities. As proof of concept, the growth assay was employed to screen a library of 1,032
Ec
FDH-H variants and reduced the library size to 96 clones. During the subsequent colorimetric screening of these clones, the variant A12G exhibiting an 82.4% enhanced formate oxidation rate was identified. Since many metal-dependent formate dehydrogenases and hydrogenases form functional complexes resembling
E. coli
FHL, the demonstrated growth-based screening strategy may be adapted to components of such electron-transferring complexes.

IMPORTANCE

Oxygen-sensitive metalloenzymes are highly potent catalysts that allow the reduction of chemically inert substrates such as CO
2
and N
2
at ambient pressure and temperature and have, therefore, been considered for the sustainable production of biofuels and commodity chemicals such as ammonia, formic acid, and glycine. A proven method to optimize natural enzymes for such applications is enzyme engineering using high-throughput variant library screening. However, most screening methods are incompatible with the oxygen sensitivity of these metalloenzymes and thereby limit their relevance for the development of biosynthetic production processes. A microtiter plate-based assay was developed for the screening of metal-dependent formate dehydrogenase that links the activity of the tested enzyme variant to the growth of the anaerobically grown host cell. The presented work extends the application range of growth-based screening to metalloenzymes and is thereby expected to advance their adoption to biosynthesis applications.
Nationwide upsurge in invasive disease in the context of longitudinal surveillance of carriage and invasive
Streptococcus pyogenes
2009–2023, the Netherlands: a molecular epidemiological study
Authors: Rümke Lidewij W. , Davies Matthew A. , Vestjens Stefan M. T. , van der Putten Boas C. L. , Bril-Keijzers Wendy C. M. , van Houten Marlies A. , Rots Nynke Y. , Wijmenga-Monsuur Alienke J. , van der Ende Arie , de Gier Brechje , Vlaminckx Bart J. M. , van Sorge Nina M.
Published: August 2024

Since 2022, many countries have reported an upsurge in invasive group A streptococcal (iGAS) infections. We explored whether changes in
Streptococcus pyogenes
carriage rates or emergence of strains with potentially altered virulence, such as
emm
1 variants M1
UK
and M1
DK
, contributed to the 2022/2023 surge in the Netherlands. We determined
emm
(sub)type distribution for 2,698 invasive and 351
S
.
pyogenes
carriage isolates collected between January 2009 and March 2023. Genetic evolution of
emm
1 was analyzed by whole-genome sequencing of 497
emm
1 isolates. The nationwide iGAS upsurge coincided with a sharp increase of
emm
1.0 from 18% (18/100) of invasive isolates in Q1 2022 to 58% (388/670) in Q1 2023 (Fisher’s exact test,
P
< 0.0001). M1
UK
became dominant among invasive
emm
1 isolates in 2016 and further expanded from 72% in Q1 2022 to 96% in Q1 2023. Phylogenetic comparison revealed evolution and clonal expansion of four new M1
UK
clades in 2022/2023. DNase Spd1 and superantigen SpeC were acquired in 9% (46/497) of
emm
1 isolates.
S. pyogenes
carriage rates and
emm
1 proportions in carriage isolates remained stable during this surge, and the expansion of M1
UK
in iGAS was not reflected in carriage isolates. During the 2022/2023 iGAS surge in the Netherlands, expansion of four new M1
UK
clades was observed among invasive isolates, but not carriage isolates, suggesting increased virulence and fitness of M1
UK
compared to contemporary M1 strains. The emergence of more virulent clades has important implications for public health strategies such as antibiotic prophylaxis for close contacts of iGAS patients.

IMPORTANCE

This study describes the molecular epidemiology of invasive group A streptococcal (iGAS) infections in the Netherlands based on >3,000
Streptococcus pyogenes
isolates from both asymptomatic carriers and iGAS patients collected before, during, and after the COVID-19 pandemic period (2009–2023) and is the first to assess whether changes in carriage rates or carried
emm
types contributed to the alarming post-COVID-19 upsurge in iGAS infections. We show that the 2022/2023 iGAS surge coincided with a sharp increase of
emm
1, particularly the toxicogenic M1
UK
variant, in invasive isolates, but not in carriage isolates. These findings suggest that increased virulence and fitness of M1
UK
likely contributes to an increased dissemination between hosts. The emergence of a more virulent and fit lineage has important implications for iGAS control interventions such as antibiotic prophylaxis for close contacts of iGAS patients and calls for a reappraisal of iGAS control interventions and guidelines.
ISGylation of the SARS-CoV-2 N protein by HERC5 impedes N oligomerization and thereby viral RNA synthesis
Authors: Zhu Junji , Liu GuanQun , Sayyad Zuberwasim , Goins Christopher M. , Stauffer Shaun R. , Gack Michaela U.
Published: August 2024

Interferon (IFN)-stimulated gene 15 (ISG15), a ubiquitin-like protein, is covalently conjugated to host immune proteins such as MDA5 and IRF3 in a process called ISGylation, thereby promoting type I IFN induction to limit the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, whether SARS-CoV-2 proteins can be directly targeted for ISGylation remains elusive. In this study, we identified the nucleocapsid (N) protein of SARS-CoV-2 as a major substrate of ISGylation catalyzed by the host E3 ligase HERC5; however, N ISGylation is readily removed through deISGylation by the papain-like protease (PLpro) activity of NSP3. Mass spectrometry analysis identified that the N protein undergoes ISGylation at four lysine residues (K266, K355, K387, and K388), and mutational analysis of these sites in the context of a SARS-CoV-2 replicon (N-4KR) abolished N ISGylation and alleviated ISGylation-mediated inhibition of viral RNA synthesis. Furthermore, our results indicated that HERC5 targets preferentially phosphorylated N protein for ISGylation to regulate its oligomeric assembly. These findings reveal a novel mechanism by which the host ISGylation machinery directly targets SARS-CoV-2 proteins to restrict viral replication and illuminate how an intricate interplay of host (HERC5) and viral (PLpro) enzymes coordinates viral protein ISGylation and thereby regulates virus replication.

IMPORTANCE

The role of protein ISGylation in regulating host cellular processes has been studied extensively; however, how ISG15 conjugation influences the activity of viral proteins, particularly coronaviral proteins, is largely unknown. Our study uncovered that the nucleocapsid (N) protein of SARS-CoV-2 is ISGylated by the HERC5 ISGylation machinery and that this modification impedes the functional assembly of N into oligomers ultimately inhibiting viral RNA synthesis. This antiviral restriction mechanism is antagonized by the PLpro deISGylation activity of SARS-CoV-2 NSP3. This study deepens our understanding of SARS-CoV-2 protein regulation by posttranslational modifications and may open new avenues for designing antiviral strategies for COVID-19.
Nectin1 is a pivotal host factor involved in attachment and entry of red-spotted grouper nervous necrosis virus in the early stages of the viral life cycle
Authors: Zhang Zhiqi , Xing Jing , Tang Xiaoqian , Sheng Xiuzhen , Chi Heng , Zhan Wenbin
Published: August 2024

Nervous necrosis virus (NNV) is a highly neurotropic virus that poses a persistent threat to the survival of multiple fish species. However, its inimitable neuropathogenesis remains largely elusive. To rummage potential partners germane to the nervous system, we investigated the interaction between red-spotted grouper NNV (RGNNV) and grouper brain by immunoprecipitation coupled with mass spectrometry and discerned Nectin1 as a novel host factor subtly involved in viral early invasion events. Nectin1 was abundant in neural tissues and implicated in the inception of tunnel nanotubes triggered by RGNNV. Its overexpression not only dramatically potentiated the replication dynamics of RGNNV in susceptible cells, but also empowered non-sensitive cells to expeditiously capture free virions within 2 min. This potency was impervious to low temperatures but was dose-dependently suppressed by soluble protein or specific antibody of Nectin1 ectodomain, indicating Nectin1 as an attachment receptor for RGNNV. Mechanistically, efficient hijacking of virions by Nectin1 strictly depended on intricate linkages to different modules of viral capsid protein, especially the direct binding between the IgC1 loop and P-domain. More strikingly, despite abortive proliferation in Nectin1-reconstructed CHSE-214 cells, a non-sensitive cell, RGNNV could gain access to the intracellular compartment by capitalizing on Nectin1, thereby inducing canonical cytoplasmic vacuolation. Altogether, our findings delineate a candidate entrance for RGNNV infiltration into the nervous system, which may shed unprecedented insights into the exploration and elucidation of RGNNV pathogenesis.

IMPORTANCE

Nervous necrosis virus (NNV) is one of the most virulent pathogens in the aquaculture industry, which inflicts catastrophic damage to ecology, environment, and economy annually around the world. Nevertheless, its idiosyncratic invasion and latency mechanisms pose enormous hardships to epidemic prevention and control. In this study, deploying grouper brain as a natural screening library, a single-transmembrane glycoprotein, Nectin1, was first identified as an emergent functional receptor for red-spotted grouper NNV (RGNNV) that widely allocated in nervous tissues and directly interacted with viral capsid protein through distinct Ig-like loops to bridge virus-host crosstalk, apprehend free virions, and concomitantly propel viral entry. Our findings illuminate the critical role of Nectin1 in RGNNV attachment and entry and provide a potential target for future clinical intervention strategies in the therapeutic race against RGNNV.
Characterization of viroplasm-like structures by co-expression of NSP5 and NSP2 across rotavirus species A to J
Authors: Lee Melissa , Cosic Ariana , Tobler Kurt , Aguilar Claudio , Fraefel Cornel , Eichwald Catherine
Published: August 2024

Rotaviruses (RVs) are classified into nine species, A–D and F–J, with species A being the most studied. In rotavirus of species A (RVA), replication occurs in viroplasms, which are cytosolic globular inclusions composed of main building block proteins NSP5, NSP2, and VP2. The co-expression of NSP5 with either NSP2 or VP2 in uninfected cells leads to the formation of viroplasm-like structures (VLSs). Although morphologically identical to viroplasms, VLSs do not produce viral progeny but serve as excellent tools for studying complex viroplasms. A knowledge gap exists regarding non-RVA viroplasms due to the lack of specific antibodies and suitable cell culture systems. In this study, we explored the ability of NSP5 and NSP2 from non-RVA species to form VLSs. The co-expression of these two proteins led to globular VLSs in RV species A, B, D, F, G, and I, while RVC formed filamentous VLSs. The co-expression of NSP5 and NSP2 of RV species H and J did not result in VLS formation. Interestingly, NSP5 of all RV species self-oligomerizes, with the ordered C-terminal region, termed the tail, being necessary for self-oligomerization of RV species A–C and G–J. Except for NSP5 from RVJ, all NSP5 interacted with their cognate NSP2. We also found that interspecies VLS are formed between closely related RV species B with G and D with F. Additionally, VLS from RVH and RVJ formed when the tail of NSP5 RVH and RVJ was replaced by the tail of NSP5 from RVA and co-expressed with their respective NSP2.

IMPORTANCE

Rotaviruses (RVs) are classified into nine species, A–D and F–J, infecting mammals and birds. Due to the lack of research tools, all cumulative knowledge on RV replication is based on RV species A (RVA). The RV replication compartments are globular cytosolic structures named viroplasms, which have only been identified in RV species A. In this study, we examined the formation of viroplasm-like structures (VLSs) by the co-expression of NSP5 with NSP2 across RV species A to J. Globular VLSs formed for RV species A, B, D, F, G, and I, while RV species C formed filamentous structures. The RV species H and J did not form VLS with their cognates NSP5 and NSP2. Similar to RVA, NSP5 self-oligomerizes in all RV species, which is required for VLS formation. This study provides basic knowledge of the non-RVA replication mechanisms, which could help develop strategies to halt virus infection across RV species.
Foot-and-mouth disease virus (FMDV) negatively regulates ZFP36 protein expression to alleviate its antiviral activity
Authors: Yin Mengge , Qian Ping , Wang Haoyuan , Zhao Qiongqiong , Zhang Huiyan , Zheng Zixuan , Zhang Min , Lu Zengjun , Li Xiangmin
Published: August 2024

Zinc finger protein 36 (ZFP36) is a key regulator of inflammatory and cytokine production. However, the interplay between swine zinc-finger protein 36 (sZFP36) and foot-and-mouth disease virus (FMDV) has not yet been reported. Here, we demonstrate that overexpression of sZFP36 restricted FMDV replication, while the knockdown of sZFP36 facilitated FMDV replication. To subvert the antagonism of sZFP36, FMDV decreased sZFP36 protein expression through its non-structural protein 3C protease (3C
pro
). Our results also suggested that 3C
pro
-mediated sZFP36 degradation was dependent on its protease activity. Further investigation revealed that both N-terminal and C-terminal-sZFP36 could be degraded by FMDV and FMDV 3C
pro
. In addition, both N-terminal and C-terminal-sZFP36 decreased FMDV replication. Moreover, sZFP36 promotes the degradation of FMDV structural proteins VP3 and VP4 via the CCCH-type zinc finger and NES domains of sZFP36. Together, our results confirm that sZFP36 is a host restriction factor that negatively regulates FMDV replication.

IMPORTANCE

Foot-and-mouth disease (FMD) is an infectious disease of animals caused by the pathogen foot-and-mouth disease virus (FMDV). FMD is difficult to prevent and control because there is no cross-protection between its serotypes. Thus, we designed this study to investigate virus-host interactions. We first demonstrate that swine zinc-finger protein 36 (sZFP36) impaired FMDV structural proteins VP3 and VP4 to suppress viral replication. To subvert the antagonism of sZFP36, FMDV and FMDV 3C
pro
downregulate sZFP36 expression to facilitate FMDV replication. Taken together, the present study reveals a previously unrecognized antiviral mechanism for ZFP36 and elucidates the role of FMDV in counteracting host antiviral activity.
Single-cell transcriptome sequencing reveals that
Wolbachia
induces gene expression changes in
Drosophila
ovary cells to favor its own maternal transmission
Authors: Miao Yun-heng , Dou Wei-hao , Liu Jing , Huang Da-wei , Xiao Jin-hua
Published: August 2024

Wolbachia
is an obligate endosymbiont that is maternally inherited and widely distributed in arthropods and nematodes. It remains in the mature eggs of female hosts over generations through multiple strategies and manipulates the reproduction system of the host to enhance its spreading efficiency. However, the transmission of
Wolbachia
within the host’s ovaries and its effects on ovarian cells during oogenesis, have not been extensively studied. We used single-cell RNA sequencing to comparatively analyze cell-typing and gene expression in
Drosophila
ovaries infected and uninfected with
Wolbachia
. Our findings indicate that
Wolbachia
significantly affects the transcription of host genes involved in the extracellular matrix, cytoskeleton organization, and cytomembrane mobility in multiple cell types, which may make host ovarian cells more conducive for the transmission of
Wolbachia
from extracellular to intracellular. Moreover, the genes
nos
and
orb
, which are related to the synthesis of ribonucleoprotein complexes, are specifically upregulated in early germline cells of ovaries infected with
Wolbachia
, revealing that
Wolbachia
can increase the possibility of its localization to the host oocytes by enhancing the binding with host ribonucleoprotein-complex processing bodies (P-bodies). All these findings provide novel insights into the maternal transmission of
Wolbachia
between host ovarian cells.

IMPORTANCE

Wolbachia
, an obligate endosymbiont in arthropods, can manipulate the reproduction system of the host to enhance its maternal transmission and reside in the host’s eggs for generations. Herein, we performed single-cell RNA sequencing of ovaries from
Drosophila melanogaster
and observed the effects of
Wolbachia
(strain
w
Mel) infection on different cell types to discuss the potential mechanism associated with the transmission and retention of
Wolbachia
within the ovaries of female hosts. It was found that the transcriptions of multiple genes in the ovary samples infected with
Wolbachia
are significantly altered, which possibly favors the maternal transmission of
Wolbachia
. Meanwhile, we also discovered that
Wolbachia
may flexibly regulate the expression level of specific host genes according to their needs rather than rigidly changing the expression level in one direction to achieve a more suitable living environment in the host’s ovarian cells. Our findings contribute to a further understanding of the maternal transmission and possible universal effects of
Wolbachia
within the host.
The impact of small intestinal bacterial overgrowth on the efficacy of fecal microbiota transplantation in patients with chronic constipation
Authors: Wang Le , Xu Yue , Li Long , Yang Bo , Zhao Di , Ye Chen , Lin Zhiliang , Cui Jiaqu , Liu Yunkun , Zhu Wanyong , Li Ning , Tian Hongliang , Chen Qiyi
Published: August 2024

To investigate the impact of Small Intestinal Bacterial Overgrowth (SIBO) on the efficacy of Fecal Microbiota Transplantation (FMT) in patients with chronic constipation, our research team included 218 patients with chronic constipation treated with FMT. Based on the results of the SIBO breath test, the patients were divided into two groups: the constipation with SIBO group (SIBO) and the constipation without SIBO group (non-SIBO). The efficacy of the two groups was evaluated using constipation-related scoring scales. At the same time, feces and small intestinal fluid samples were collected from both groups before and after FMT to compare the changes in the intestinal microbiota through 16S rRNA sequencing. In this study, it was found that the clinical efficacy of FMT in the SIBO group was superior to that in the non-SIBO group. After FMT treatment, both groups showed a significant increase in bowel frequency and improvement in stool characteristics. Abdominal symptoms, rectal symptoms, and defecation symptoms were significantly alleviated (
P
< 0.05), and patients’ quality of life was significantly enhanced (
P
< 0.05). After FMT, except for the Constipation Assessment Scale scores, other scale scores showed significant differences between the two groups, the SIBO group scoring significantly better than the non-SIBO group (
P
< 0.05). After FMT, there were minor changes in the colonic microbiota but more substantial changes in the small intestinal microbiota. At baseline, the SIBO group had a higher abundance of
Veillonella
, and lower abundances of
Escherichia-Shigella
and
Acinetobacter
compared to the non-SIBO group. Chronic constipation patients with SIBO have a better response to FMT than those without SIBO.

IMPORTANCE

Existing studies have rarely considered the impact of the small intestine’s microbial state on the efficacy of fecal microbiota transplantation (FMT), nor have they extensively explored the effect of the small intestine’s microbial state on the recovery of colonic motility. Therefore, this study investigates the influence of small intestinal bacterial overgrowth (SIBO) on the efficacy of FMT in treating constipation, specifically the impact of the microbial state of the small intestine on the restoration of colonic homeostasis, and consequently on the recovery of colonic motility.
The role of exopolysaccharides Psl and Pel in resistance of
Pseudomonas aeruginosa
to the oxidative stressors sodium hypochlorite and hydrogen peroxide
Authors: da Cruz Nizer Waleska S. , Allison Kira N. , Adams Madison E. , Vargas Mario A. , Ahmed Duale , Beaulieu Carole , Raju Deepa , Cassol Edana , Howell P. Lynne , Overhage Joerg
Published: August 2024

Pseudomonas aeruginosa
is well-known for its antimicrobial resistance and the ability to survive in harsh environmental conditions due to an abundance of resistance mechanisms, including the formation of biofilms and the production of exopolysaccharides. Exopolysaccharides are among the major components of the extracellular matrix in biofilms and aggregates of
P. aeruginosa
. Although their contribution to antibiotic resistance has been previously shown, their roles in resistance to oxidative stressors remain largely elusive. Here, we studied the function of the exopolysaccharides Psl and Pel in the resistance of
P. aeruginosa
to the commonly used disinfectants and strong oxidizing agents NaOCl and H
2
O
2
. We observed that the simultaneous inactivation of Psl and Pel in
P. aeruginosa
PAO1 mutant strain ∆
pslA pelF
resulted in a significant increase in susceptibility to both NaOCl and H
2
O
2
. Further analyses revealed that Pel is more important for oxidative stress resistance in
P. aeruginosa
and that the form of Pel (i.e., cell-associated or cell-free) did not affect NaOCl susceptibility. Additionally, we show that Psl/Pel-negative strains are protected against oxidative stress in co-culture biofilms with
P. aeruginosa
PAO1 WT. Taken together, our results demonstrate that the EPS matrix and, more specifically, Pel exhibit protective functions against oxidative stressors such as NaOCl and H
2
O
2
in
P. aeruginosa
.

IMPORTANCE

Biofilms are microbial communities of cells embedded in a self-produced polymeric matrix composed of polysaccharides, proteins, lipids, and extracellular DNA. Biofilm bacteria have been shown to possess unique characteristics, including increased stress resistance and higher antimicrobial tolerance, leading to failures in bacterial eradication during chronic infections or in technical settings, including drinking and wastewater industries. Previous studies have shown that in addition to conferring structure and stability to biofilms, the polysaccharides Psl and Pel are also involved in antibiotic resistance. This work provides evidence that these biofilm matrix components also contribute to the resistance of
Pseudomonas aeruginosa
to oxidative stressors including the widely used disinfectant NaOCl. Understanding the mechanisms by which bacteria escape antimicrobial agents, including strong oxidants, is urgently needed in the fight against antimicrobial resistance and will help in developing new strategies to eliminate resistant strains in any environmental, industrial, and clinical setting.
Evaluation of the quickmic system in the rapid diagnosis of Gram-negative bacilli bacteremia
Authors: García-Rivera Celia , Ricart-Silvestre Andrea , Parra Grande Mónica , Ventero María Paz , Tyshkovska-Germak Iryna , Sánchez-Bautista Antonia , Merino Esperanza , Rodríguez Juan Carlos
Published: August 2024

Rapid microbiological diagnosis of the antibiotic susceptibility of Gram-negative bacilli is a priority in clinical microbiology, especially in cases of bacteremia. The rapid advancement of antimicrobial resistance proposes a challenge for empirical antibiotic therapy and shows the need for fast antibiotic susceptibility diagnostics to guide treatments. The QuickMIC System (Gradientech AB, Uppsala, Sweden) is a recently developed rapid diagnostic tool for antibiotic susceptibility testing. Our study evaluates a rapid phenotypic system (QuickMIC) that provides information on the susceptibility of 12 antibiotics against
Escherichia coli
,
Klebsiella spp
.,
Pseudomonas aeruginosa
,
Acinetobacter baumannii
,
Enterobacter cloacae
,
Proteus spp
.,
Citrobacter spp.,
and
Serratia marcescens
. A total of 816 antibiotic/microorganism combinations were tested, resulting in eight discrepancies. The concordance between the antibiotics offered by QuickMIC and reference methods (MicroScan WalkAway plus system, Beckman Coulter; Etest (BioMerieux microdilution system (Bruker); Real-time PCR (GeneXpert, Cepheid); and immunochromatography (Biotech) was 99.02%. Time elapsed to obtain a valid minimal inhibitory concentration (MIC) was between 2 and 4 h. The QuickMIC system allows for the early adjustment of antibiotic treatment in these infections. Given the existing limitations of currently available rapid methods, its clinical utility is particularly relevant in the management of
P. aeruginosa
infections and AmpC-producing Enterobacterales. The use of rapid methods can help diversify antibiotic use and reduce carbapenem consumption.

IMPORTANCE

The rapid diagnosis of antibiotic sensitivity in Gram-negative bacilli is of paramount importance in clinical microbiology, particularly in cases of bacteremia. The escalating challenge of antimicrobial resistance underscores the need for expeditious antibiotic susceptibility diagnostics to guide empirical antibiotic therapy effectively. In light of this, we present our study that evaluates the QuickMIC System, a recently developed rapid diagnostic antibiogram. QuickMIC System, offers a novel approach to phenotypic testing, providing information on the activity of 12 antibiotics against key pathogens, including
Escherichia coli
,
Klebsiella spp
.,
Pseudomonas aeruginosa
,
Acinetobacter baumannii
,
Enterobacter cloacae
,
Proteus spp
.,
Citrobacter spp
., and
Serratia marcescens
. Our investigation involved testing a total of 816 antibiotic/microorganism combinations. The study demonstrated an impressive 99.02% concordance between the QuickMIC System and the reference methods, with only eight discrepancies observed. The time to actionable minimum inhibitory concentration (MIC) ranged between 2 and 4 h, highlighting the system's efficiency in providing rapid results.
IOC consensus statement on elite youth athletes competing at the Olympic Games: essentials to a healthy, safe and sustainable paradigm
Authors: Bergeron Michael F , Côté Jean , Cumming Sean P , Purcell Rosemary , Armstrong Neil , Basilico Luca , Burrows Kirsty , Charrin Jean-Benoit , Felix Allyson , Groesswang Heike , Iwasaki Yasunobu , Kocher Mininder S , Martowicz Magali , McConnell Kit , Moran Jane , Holm Moseid Christine , Mountjoy Margo , Soligard Torbjørn , Tetelbaum Evgenia , Thiel Ansgar , Vertommen Tine , Viseras Gloria , Budgett Richard , Engebretsen Lars , Erdener Uğur
Published: August 2024

With the pronounced ongoing growth of global youth sports, opportunities for and participation of youth athletes on the world sports stage, including the Olympic Games, are expected to escalate. Yet, adolescence is a vulnerable period of development and inherently dynamic, with non-linear and asynchronous progression of physical, physiological, psychological and social attributes. These non-concurrent changes within and between individuals are accompanied by irregular and unpredictable threats and impediments. Likewise, the evident age-based criteria and conventional path for those youth athletes deemed eligible candidates for the Olympic Games are not well or consistently defined. Furthermore, the unstructured and largely varying policies and practices across the sporting International Federations specific to youth participation underscore the need to establish a contemporary universal paradigm that would enable elite youth athletes to navigate an individualised healthy pathway to personal, athletic and sport success. First, we reviewed and summarised key challenges facing elite youth athletes and the relevant evidence fundamental to facilitating and supporting central aspects of health and well-being, while empowering safe, sustainable and positive engagement during athletic and personal advancement and competition. Second, we developed and present a modern elite youth athlete model that emphasises a child-centred, practical framework with corresponding guidelines and recommendations to protect health and well-being while safely and favourably managing international sport competition. Our proposed evidence-informed paradigm will enable and support individualised pathways for healthy, well-rounded and sustainable positive engagement while achieving sport success for youth contending or aiming to compete at world-class international sporting events.
The physiological consequences of and recovery following the Australian Special Forces Selection Course
Authors: Uphill Angela C. , Kendall Kristina L. , Baker Bradley A. , Guppy Stuart N. , Brown Hannah M. , Vacher Michael , Nindl Bradley C. , Haff G. Gregory
Published: August 2024

This study aimed to determine the energy requirements, physiological consequences, and recovery rate from the Australian Special Forces Selection Course. Ninety-three male soldiers (mean ± SD, 28.1 ± 3.6 years, 1.81 ± 0.1 m, 85.1 ± 8.1 kg) volunteered for this study. Body composition via dual-energy X-ray absorptiometry, hormones and resting metabolic rate were assessed before, immediately after, and at 1, 3, 5, and 8 weeks post-course. Energy expenditure, assessed via doubly-labelled water during the first 10 days of the course significantly exceeded energy intake (expenditure: 7680 ± 1095 kcal.day–1, intake: 3859 ± 704 kcal.day –1). Body mass (Δ –6.8 ± 1.9 kg, p < 0.01), fat mass (Δ –4.2 ± 1.0 kg, p < 0.0001) and lean mass (Δ –3.0 ± 1.7 kg, p < 0.0001) were significantly reduced in response to the course and returned to baseline 1–3 weeks post-course. Total testosterone, free testosterone, free triiodothyronine, free thyroxine and insulin like growth factor-1 significantly ( p < 0.001) declined following the course, while cortisol and sex hormone binding globulin increased ( p < 0.001). All hormones, except insulin like growth factor-1, returned to baseline concentrations within 1–3 weeks post-course. Resting metabolic rate decreased ( p < 0.01) in response to the course, and subsequently rebounded above baseline levels at 1 week post-course. The Special Forces Selection Course involved high energy output and a substantial caloric deficit, resulting in body mass loss and significant hormonal disruption that took weeks to recover. These results highlight the energy requirements, physiological consequences, and recovery processes from the Australian Special Forces Selection Course.
Why Do Chinese and Indian Positions on Climate Differ? Labor Surplus Absorption as a Key Factor
Authors: BERTHAUD PIERRE , FONTANA YANN , GUILHOT LAËTITIA
Published: August 2024

During international negotiations for the Rio Earth Summit of 1992, coalitions made up of countries from the Global South took shape, only to break up gradually over time. The climate positions of two leading emerging powers, the People’s Republic of China and India, have increasingly drifted apart from each other since 2010. This paper seeks to account for this drift by relying on structural factors. The analytical framework proposed here relies on three structural determinants of development: factor endowments, sector specialization, and labor surplus absorption potential. These determinants are complemented by a carbon variable to account for sustainability. This framework reveals a triangle of incompatibility between development, labor surplus absorption, and sustainability that highlights how the People’s Republic of China now has sufficient leeway to engage in more ambitious sustainable policies, while India still faces the mutual incompatibility of either pushing forward with economic development or committing to a sustainable agenda.
Insight of Chinese Herbal Medicine in Treating Osteoporosis: Achievements from 2013 to 2023
Authors: Tan Mingshuai , Li Qiang , Yang Bencheng , Wang Sihan , Chen Ze
Published: August 2024

Osteoporosis is the most common bone metabolic disease, and it is becoming increasingly common as the global population ages. Osteoporosis and its complications, such as fractures and pain, negatively affect patient quality of life and easily lead to disability, placing enormous burdens on society. Although several anti-osteoporosis drugs are currently available, many adverse reactions have been observed during the long-term application of these drugs. Therefore, safer and more useful medications are urgently needed to replace those currently available. Chinese herbal medicine has been extensively used to treat osteoporosis, and the current literature confirms that such medicines have anti-osteoporosis effects, are safe, and have minimal side effects. Thus, Chinese herbal medicines are natural alternatives to pharmaceutical approaches to treating osteoporosis, and these medicines must be further developed and utilized. In this article, we review the mechanisms underlying the anti-osteoporosis effects of single herbal extracts and traditional Chinese medicine (TCM) formulas that have been elucidated since 2013, providing key evidence and support for future research on the anti-osteoporosis effects of Chinese herbal medicines. In addition, due to the complexity of the ingredients in Chinese herbal medicine, more thorough investigations are needed to determine the specific ingredients that are effective in osteoporosis treatment. Therefore, identifying the effective ingredients of Chinese herbal medicines will be a necessary focus in laboratory research and clinical application.
Atractylodin: An Alkyne Compound with Anticancer Potential
Authors: Zhong Wenxia , Zhang Qi
Published: August 2024

Atractylodin is one of the main active ingredients of Atractylodis Rhizoma. It has various pharmacological properties, such as antigastric ulcer, immune regulation, antibacterial, anti-inflammatory, antitumor, anti-oxidant, and neuroprotective properties. In the past few decades, atractylodin has attracted the attention of researchers due to its excellent therapeutic effects. This paper aims to review the pharmacology of atractylodin, focusing mainly on its pharmacological effects in tumor treatment. Atractylodin exerts its antitumor effect by regulating different signaling pathways to induce important biological events such as apoptosis, cell cycle arrest, and autophagy, inhibiting cancer cell invasion and metastasis. In the process of cell apoptosis, atractylodin mainly induces cancer cell apoptosis by downregulating the Notch signaling pathway, affecting multiple upstream and downstream targets. In addition, atractylodin induces autophagy in cancer cells by regulating various signaling pathways such as PI3K/AKT/mTOR, p38MAPK, and hypothalamic Sirt1 and p-AMPK. Atractylodin effectively induces G1/M and G2/M phase arrest under the action of multiple signaling pathways. Among them, the pathways related to G1/M are more widely stagnated. In inhibiting the migration and invasion of cancer cells, atractylodin mainly regulates the Wnt signaling pathway, downregulates the expression of N-cadherin in cancer cells, and then blocks the PI3K/AKT/mTOR signaling pathway, inhibiting the phosphorylation of PI3K, AKT, and mTOR proteins, thereby having a significant impact on the invasion and migration of cancer cells. This paper systematically reviews the research progress on the antitumor effects and mechanisms of atractylodin, hoping to provide a reference and theoretical basis for its clinical application and new drug development.
Dynamic Analysis of the Multichannel Supply Chain Under Carbon Subsidy Policy
Authors: Tian Yi , Liu Qiang , Wu Yongchun , Geng Liyan
Published: August 2024

For achieving the goals of carbon peaking and carbon neutrality, the government will further strengthen subsidies to enterprises for carbon emission reduction. This paper investigates the long-term repeated game behavior of manufacturer and retailer in multichannel supply chains under three different forms of government subsidies. The long-term repeated game behavior of manufacturer and retailer is studied under the manufacturer green innovation subsidy model (IS model), manufacturer production subsidy model (MS model) and retailer sales subsidy model (RS model). Under three situations, excessive price adjustment can easily lead to system instability and sharp fluctuations in profits. Two methods are used for chaos control and management, and the parameter adjustment control method is found having more advantages for system re-stabilization.
THE EDGEWORTH AND GRAM–CHARLIER DENSITIES
Authors: ASCHAKULPORN PAKORN , ZHANG JIN E.
Published: August 2024

This paper is the first to define the Edgeworth density and comprehensively compare it to the Gram–Charlier density in the context of option pricing. The two densities allow additional cumulants to the normal distribution; although similar, they are not the same when truncated. Many academics have misidentified the two. This paper clearly distinguishes the two, presents the derivation of both, and develops a general option pricing model which can be used for both densities with an arbitrary number of additional cumulants. The option pricing formula for each density is also calibrated and compared to more typical models with the most advanced being the affine jump-diffusion model (stochastic volatility with double jumps).
Approximation of neural network operators based on the Joukowski transformation
Authors: Jin Mingwei , Xiang Daode , Yu Dansheng
Published: August 2024

The properties of activation functions profoundly affect the approximation performance of neural networks. It is always one of the most important tasks to find proper activation functions in approximation by neural networks for some specific purpose. In this paper, we introduce a new activation function which is generated by the Joukowski transformation, and construct some new neural network operators activated by the new activation function. We show that the new neural network operators can be used to approximate the continuous functions on some compact sets. In fact, we give the approximation rate by using the modulus of continuity of the objective function (see Theorem 1). Finally, we provide some specific numerical examples to verify the fitting effects of the neural network operators with different parameters for continuous functions.
Sustainability of the Urban System Planning in Shu City, Kazakhstan: An Evaluation through Residents’ Perception
Authors: SAKHATBEKOVNA Turdanova Malika , KAMANAEVNA Muzdybayeva Karlygash , AKBAR Imanaly , ZHAKSYBEKKYZY Tazhekova Akmaral , KAZBEKKYZY Myrzaliyeva Zabira
Published: August 2024

It is important to consider the local people’s evaluation in increasing the effectiveness of the sustainable planning process in urban system planning. In this work, the sustainability of urban system planning in Shu city of Kazakhstan is evaluated according to the defined dimensions, which play a key role in determining the population’s living standard, and the indicators of each dimension are compared. The data are obtained mainly through the household questionnaire survey, field observations, in depth interviews, and focus group discussion. In total, 832 representative respondents were surveyed with five-point Likert scale questions in this paper. The study used 42 indicators based on six dimensions: environmental, social, cultural, economic, religious/spiritual, and institutional dimensions. The results of this analysis show that the sustainability level of urban system planning in Shu city is at a low level in all six dimensions. The results of the indicator analysis show that the people of this region are generally not satisfied with the solution of some environmental, social, and economic problems in Shu city. At the same time, residents rated the indicators of institutional stability as better, on the contrary, they rated cultural and religious/spiritual indicators relatively high. As a result, we initially asserted that the sustainability of the urban system planning in Shu city is not satisfactory considering the existing possibilities. To eliminate this shortcoming, the authorities responsible for planning the urban system should jointly develop a project policy for sustainable development with all interested parties.
Moving from Theory to Application: Black Feminist Thought as an Intersectional Framework for Design
Authors: Rankin Yolanda
Published: August 2024

In this forum we explore different perspectives for how to apply intersectionality as a critical framework for design across multiple contexts. ---
Yolanda A. Rankin and Jakita O. Thomas, Editors